Kramer’s father, older brother Arthur, and two uncles were alumni of Yale University. Kramer enrolled at Yale in 1953, where he had difficulty adjusting. He felt lonely, and earned lower grades than those to which he was accustomed. He attempted suicide by an overdose of aspirin because he felt like he was the “only gay student on campus”. The experience left him determined to explore his sexuality and set him on the path to fight “for gay people’s worth”. The next semester, he had an affair with his German professor – his first requited romantic relationship with a man. Kramer enjoyed the Varsity Glee Club during his remaining time at Yale, and he graduated in 1957 with a degree in English. He served in the U.S. Army Reserve before beginning his film writing and production career.

Kramer then began to integrate homosexual themes into his work, and tried writing for the stage. He wrote Sissies’ Scrapbook in 1973 (later rewritten and retitled as Four Friends), a dramatic play about four friends, one of whom is gay, and their dysfunctional relationships. Kramer called it a play about “cowardice and the inability of some men to grow up, leave the emotional bondage of male collegiate camaraderie, and assume adult responsibilities”. The play was first produced in a theater set up in an old YMCA gymnasium on 53rd Street and Eighth Avenue called the Playwrights Horizons. Live theater moved him to believing that writing for the stage was what he wanted to do. Although the play was given a somewhat favorable review by The New York Times, it was closed by the producer and Kramer was so distraught that he decided never to write for the stage again, later stating, “You must be a masochist to work in the theater and a sadist to succeed on its stages.”

In 1978, Kramer delivered the final of four drafts of a novel that he wrote about the fast lifestyle of the gay men on Fire Island and in Manhattan. In Faggots, the primary character was modeled on himself, a man who is unable to find love while encountering the drugs and emotionless sex in the trendy bars and discos. He stated his inspiration for the novel: “I wanted to be in love. Almost everybody I knew felt the same way. I think most people, at some level, wanted what I was looking for, whether they pooh-poohed it or said that we can’t live like the straight people or whatever excuses they gave.” Kramer researched the book, talking to many men, and visiting various establishments. As he interviewed people, he heard a common question: “Are you writing a negative book? Are you going to make it positive? … I began to think, ‘My God, people must really be conflicted about the lives they’re leading.’ And that was true. I think people were guilty about all the promiscuity and all the partying.”

However, when friends he knew from Fire Island began getting sick in 1980, Kramer became involved in gay activism. In 1981, although he had not been involved previously with gay activism, Kramer invited the “A-list” (his own term) group of gay men from the New York City area to his apartment to listen to a doctor say their friends’ illnesses were related, and research needed to be done. The next year, they named themselves the Gay Men’s Health Crisis (GMHC) and became the primary organization to raise funds for and provide services to people stricken with Acquired Immune Deficiency Syndrome (AIDS) in the New York area. Although Kramer served on its first board of directors, his view of how it should be run sharply conflicted with that of the rest of its members. While GMHC began to concentrate on social services for men who were dying, Kramer loudly insisted they fight for funding from New York City. Mayor Ed Koch became a particular target for Kramer, as did the behavior of gay men, before the nature of how the Human Immunodeficiency Virus (HIV) was transmitted was understood.

Around 1981, Kramer began researching and writing a manuscript called The American People: A History, an ambitious historical work that begins in the Stone Age and continues into the present. For example, there is information relating to Kramer’s assertion that Abraham Lincoln was gay. In 2002, Will Schwalbe, editor-in-chief of Hyperion Books – the only man to have read the entire manuscript to that date – said, “He has set himself the hugest of tasks,” and he described it as “staggering, brilliant, funny, and harrowing.” In 2006, Kramer said of the work, “[It is] my own history of America and of the cause of HIV/AIDS … Writing and researching this history has convinced me that the plague of HIV/AIDS has been intentionally allowed to happen.”

When doctors suggested men stop having sex, Kramer strongly encouraged GMHC to deliver the message to as many gay men as possible. When they refused, Kramer wrote an essay entitled “1,112 and Counting”, which appeared in 1983 in the New York Native, a gay newspaper. The essay discussed the spread of the disease, the lack of government response, and the apathy of the gay community. The essay was intended to frighten gay men and provoke them to protest government indifference. Michael Specter wrote in The New Yorker, “it was a five-thousand-word screed that accused nearly everyone connected with health care in America – officials at the Centers for Disease Control, in Atlanta, researchers at the National Institutes of Health, in Washington D.C., doctors at Memorial Sloan-Kettering Cancer Center, in Manhattan, and local politicians (particularly Mayor Ed Koch) – of refusing to acknowledge the implications of the nascent AIDS epidemic. The article’s harshest condemnation was directed at those gay men who seemed to think that if they ignored the new disease, it would simply go away. Tony Kushner, who won the 1993 Pulitzer Prize for Drama for his play Angels in America about the impact of AIDS in the United States, described the essay as “With that one piece, Larry changed my world. He changed the world for all of us.”

Kramer’s past also compromised his message, as many men who had been turned off by Faggots saw Kramer’s warnings as alarmist, displaying negative attitudes toward sex. Playwright Robert Chesley responded to Kramer’s New York Native article, saying, “Read anything by Kramer closely, and I think you’ll find the subtext is always: the wages of gay sin are death”. The GMHC ousted Kramer from the organization in 1983. Kramer’s preferred method of communication was deemed too militant for the group.

Kramer’s relationship with his brother, Arthur Kramer, founding partner of the law firm Kramer Levin, was portrayed in Kramer’s 1984 play, The Normal Heart. In the play, Kramer represents Arthur (as Ben Weeks) as more concerned with building his $2 million house in Connecticut than in helping his brother’s cause. Humorist Calvin Trillin, a friend of both Larry and Arthur, once called The Normal Heart “the play about the building of [Arthur’s] house”. Anemona Hartocollis observed in The New York Times that “their story came to define an era for hundreds of thousands of theatergoers”. Arthur, who had protected his younger brother from the parents they both disliked, could neither reject Larry, nor accept his homosexuality. This caused years of arguing and stretches of silence between them. In the 1980s, Arthur refused Larry’s request that his firm represent the fledgling Gay Men’s Health Crisis, blaming the need to clear it with his firm’s intake committee. Larry called upon gays to boycott MCI, a prominent Kramer Levin client, which Arthur viewed as a personal affront. In 1992, after Colorado voters endorsed an anti-gay rights referendum, Larry supported a boycott of the state while Arthur refused to cancel a ski trip to Aspen.

The Normal Heart is a play set between 1981 and 1984. It addresses a writer named Ned Weeks as he nurses his lover, who is dying of an unnamed disease. His doctors are puzzled and frustrated by having no resources to research it. Meanwhile, the unnamed organization Weeks is involved in is angered by the bad publicity Weeks’ activism is generating, and eventually throws him out. Kramer later explained, “I tried to make Ned Weeks as obnoxious as I could … I was trying, somehow and again, to atone for my own behavior.” The experience was overwhelmingly emotional for Kramer, as at one time during rehearsals he watched actor Brad Davis hold his dying lover played by D. W. Moffett on stage; Kramer went into the bathroom and sobbed, only moments later to find Davis holding him. The play is considered a literary landmark. It contended with the AIDS crisis when few would speak of the disease afflicting gay men, including gays themselves; it remains the longest-running play ever staged at the Public Theater, running for a year starting in 1985. It has been produced over 600 times in the U.S., Europe (where it was televised in Poland), Israel, and South Africa. Polish television adaptation débuted on the TVP channel on 4 May 1989, one month before the first free election in the country since 1928.

In 1987, Kramer was the catalyst in the founding of the AIDS Coalition to Unleash Power (ACT UP), a direct action protest organization that chose government agencies and corporations as targets to publicize lack of treatment and funding for people with AIDS. ACT UP was formed at the Lesbian, Gay, Bisexual and Transgender Community Services Center in New York City. Kramer was asked to speak as part of a rotating speaker series, and his well-attended speech focused on action to fight AIDS. He began by having two-thirds of the room stand up, and told them they would be dead in five years. Kramer reiterated the points introduced in his essay “1,112 and Counting”: “If my speech tonight doesn’t scare the shit out of you, we’re in real trouble. If what you’re hearing doesn’t rouse you to anger, fury, rage, and action, gay men will have no future here on earth. How long does it take before you get angry and fight back?” Their first target became the Food and Drug Administration (FDA), which Kramer accused in The New York Times of neglecting badly needed medication for HIV-infected Americans.

Engaging in civil disobedience that would result in many people being arrested was a primary objective, as it would focus attention on the target. On March 24, 1987, 17 people out of 250 participating were arrested for blocking rush-hour traffic in front of the FDA’s Wall Street offices. Kramer was arrested dozens of times working with ACT UP, and the organization grew to hundreds of chapters in the U.S. and Europe. Immunologist Anthony Fauci stated, “In American medicine there are two eras. Before Larry and after Larry.” Playwright Tony Kushner offered his opinion of why Kramer fought so relentlessly: “In a way, like a lot of Jewish men of Larry’s generation, the Holocaust is a defining historical moment, and what happened in the early 1980s with AIDS felt, and was in fact, holocaustal to Larry.”

Continuing his commentary on government indifference toward AIDS, Kramer wrote Just Say No, A Play about a Farce in 1988. In the dramatic work he highlighted the sexual hypocrisy in the Reagan and Koch administrations that allowed AIDS to become an epidemic; it concerns a First Lady, her gay son, and the closeted gay mayor of America’s “largest northeastern city”. Its New York production, starring Kathleen Chalfant, Tonya Pinkens, and David Margulies, was prized by the few who came to see it after its negative review by The New York Times. Social critic and writer Susan Sontag wrote of the piece, “Larry Kramer is one of America’s most valuable troublemakers. I hope he never lowers his voice.”

In 1988, stress over the closing of his play Just Say No, only a few weeks after its opening, forced Kramer into the hospital after it aggravated a congenital hernia. While in surgery, doctors discovered liver damage due to Hepatitis B, prompting Kramer to learn that he was HIV positive. In 2001, at the age of 66, Kramer was in dire need of a liver transplant, but he was turned down by Mount Sinai Hospital’s organ transplant list. People living with HIV were routinely considered inappropriate candidates for organ transplants because of complications from HIV and perceived short lifespans. Out of the 4,954 liver transplants performed in the United States, only 11 were for HIV-positive people. The news prompted Newsweek to announce Kramer was dying in June 2001; the Associated Press in December of the same year reported Kramer’s death. Kramer became a symbol for infected people who had new leases on life due to advances in medicine. “We shouldn’t face a death sentence because of who we are or who we love”, he said in an interview. In May 2001, the Thomas E. Starzl Transplantation Institute at the University of Pittsburgh, which had performed more transplants for HIV positive patients than any other facility in the world, accepted Kramer as a potential transplant recipient. Kramer received a new liver on December 21, 2001. In April 2019 he suffered a broken leg.

First published in 1989, and later expanded and republished in 1994, Reports from the Holocaust: The Making of an AIDS Activist contains a diverse selection of the non-fiction writings of Larry Kramer focused on AIDS activism and LGBT civil rights, including letters to the editor and speeches, which document his time spent at Gay Men’s Health Crisis, ACT UP, and beyond, with the updated edition being organised chronologically from 1978 to 1993.

Kramer divided his time between a residence in Manhattan, near Washington Square Park in Greenwich Village, and Connecticut. Another resident of Kramer’s Manhattan residential complex was Kramer’s longtime nemesis, Ed Koch, who had been mayor of New York City from 1978 to 1989. The two saw each other relatively infrequently, since they lived in different towers. When Kramer saw Koch looking at the apartment in 1989, Kramer reportedly told him, “Don’t move in here! There are people here who hate you!” On another occasion, Koch tried to pet Kramer’s Wheaten Terrier dog, Molly, in the building’s mail area, and Kramer snatched the dog away, telling her that Koch was “the man who killed all of Daddy’s friends.”

The Destiny of Me picks up where The Normal Heart left off, following Ned Weeks as he continues his journey fighting those whose complacency or will impede the discovery of a cure for a disease from which he suffers. The play opened in October 1992 and ran for one year off Broadway at the Lucille Lortel Theatre by the Circle Repertory Company. It was a finalist for the Pulitzer Prize, was a double Obie Award winner and received the Lortel Award for Outstanding Play of the Year. The original production starred John Cameron Mitchell, “a young actor who dominates the show with a performance at once ethereal and magnetic”, according to The New York Times reviewer Frank Rich. Most powerful, Rich wrote, was the thematic question Kramer posed to himself: “Why was he of all people destined to scream bloody murder with the aim of altering the destiny of the human race?” Kramer states in his introduction to the play:

Kramer Levin went on to become one of the gay rights movement’s staunchest advocates, helping Lambda Legal Defense and Education Fund on such high-profile cases as Lawrence v. Texas before the U.S. Supreme Court and Hernandez v. Robles before the New York Court of Appeals. Arthur Kramer retired from the firm in 1996 and died from a stroke in 2008.

In 1997, Kramer approached Yale University, to bequeath several million dollars “to endow a permanent, tenured professorship in gay studies and possibly to build a gay and lesbian student center.” At that time, gender, ethnic and race-related studies were viewed warily by academia. The then Yale provost, Alison Richard, stated that gay and lesbian studies was too narrow a specialty for a program in perpetuity. Kramer’s rejected proposal read: “Yale is to use this money solely for 1) the study of and/or instruction in gay male literature, by which I mean courses to study gay male writers throughout history or the teaching to gay male students of writing about their heritage and their experience. To ensure for the continuity of courses in either or both of these areas tenured positions should be established; and/or 2) the establishment of a gay student center at Yale.”

In 2000, Reynolds Price wrote that the novel’s lasting relevance is that “anyone who searches out present-day responses on the Internet will quickly find that the wounds inflicted by Faggots are burning still”. Although the novel was rejected by the people from whom Kramer expected praise, the book has never been out of publication and is often taught in gay studies classes. “Faggots struck a chord,” wrote Andrew Sullivan, “It exuded a sense that gay men could do better if they understood themselves as fully human, if they could shed their self-loathing and self-deception….”

In 2001, both sides settled upon establishing the Larry Kramer Initiative for Lesbian and Gay Studies, which would include visiting professors and a program of conferences, guest speakers and other events. Arthur Kramer endowed the program at Yale with $1 million to support a five-year trial. Kramer agreed to leave his literary papers and those chronicling the AIDS movement and his founding of GMHC and ACT UP to Yale’s Beinecke Library. “A lot has changed since I made my initial demands,” said Kramer. “I was trying to cram stuff down their throat. I’d rather they fashion their own stuff. It may allow for a much more expandable notion of what lesbian and gay studies really is.” The five-year program ended in 2006.

In 2001, Arthur gave Yale a $1 million grant to establish the Larry Kramer Initiative for Lesbian and Gay Studies, a program focusing on gay history.

Its 2002 London Finborough Theatre production was the No. 1 Critics Choice in The Evening Standard.

Two decades later Kramer continued to advocate for social and legal equity for homosexuals. “Our own country’s democratic process declares us to be unequal, which means, in a democracy, that our enemy is you,” he wrote in 2007. “You treat us like crumbs. You hate us. And sadly, we let you.”

Kramer and his partner, architectural designer David Webster, were together from 1991 until Kramer’s death. Webster’s ending of his relationship with Kramer in the 1970s had inspired Kramer to write Faggots (1978). When asked about their reunion decades later, Webster replied: “He’d grown up, I’d grown up.” On July 24, 2013, Kramer and Webster married in the intensive care unit of NYU Langone Medical Center in New York City while Kramer recovered from surgery.

In 2014, HBO produced a film version directed by Ryan Murphy with a screenplay by Kramer. It starred Mark Ruffalo, Matt Bomer (who won a Golden Globe Award for his performance), Taylor Kitsch, Jim Parsons, Alfred Molina, Julia Roberts, Joe Mantello, Jonathan Groff, and BD Wong.

The book was published as a novel by Farrar, Straus & Giroux in 2015. In The New York Times Book Review, Dwight Garner wrote, “I wish I could report that The American People, Volume 1 had power to match its scope. It does not. As a work of sustained passion, it is formidable. As a work of art, it is very modest indeed. The tone is talky and digressive; few real characters emerge; one feels lashed to the mast after only 50 pages or so.” In the book, Kramer writes that in addition to Abraham Lincoln, George Washington, Benjamin Franklin, Alexander Hamilton, Andrew Jackson, Franklin Pierce, James Buchanan, Mark Twain, Herman Melville, and Richard Nixon were gay. The second volume, 880 pages, was published in 2020.

In 2020, in response to the COVID-19 pandemic, Kramer began to write a play titled An Army of Lovers Must Not Die.

Kramer died of pneumonia on May 27, 2020, at age 84, less than a month short of his 85th birthday.