Koch attended the Deerfield Academy prep school in Massachusetts, graduating in 1959. He attended Massachusetts Institute of Technology (MIT), earning both a bachelor’s (1962) and a master’s degree (1963) in chemical engineering. He was a member of the Beta Theta Pi fraternity. Koch played basketball at MIT, averaging 21 points per game at MIT over three years, a school record. He also held the single-game scoring record of 41 points from 1962 until 2009, when it was eclipsed by Jimmy Bartolotta.

In 1970, Koch joined Koch Industries under his brother Charles, to work as a technical-services manager. He founded the company’s New York City office and in 1979 he became the president of his own division, Koch Engineering, renamed Chemical Technology Group. David’s brothers Frederick and Bill had inherited stock in Koch Industries. In June 1983, after a bitter legal and boardroom battle, the stakes of Frederick and Bill were bought out for $1.1 billion and Charles Koch and David Koch became majority owners in the company. Legal disputes against Charles and David lasted roughly two decades. Frederick and Bill sided with J. Howard Marshall III, J. Howard Marshall II’s eldest son, against Charles and David at one point, in order to take over the company. In 2001, Bill reached a settlement in a lawsuit where he had charged the company was taking oil from federal and Indian land; that settlement ended all litigation between the brothers. CBS News reported that Koch Industries settled for $25 million.

Koch was the Libertarian Party’s vice-presidential candidate in the 1980 presidential election, sharing the party ticket with presidential candidate Ed Clark. The Clark–Koch ticket promised to abolish Social Security, the Federal Reserve Board, welfare, minimum-wage laws, corporate taxes, all price supports and subsidies for agriculture and business, and U.S. Federal agencies including the SEC, EPA, ICC, FTC, OSHA, FBI, CIA, and DOE. The ticket received 921,128 votes, 1% of the total nationwide vote, the Libertarian Party national ticket’s best showing until 2016 in terms of percentage and its best showing in terms of raw votes until the 2012 presidential election, although that number was surpassed again in 2016. “Compared to what [the Libertarians had] gotten before,” Charles said, “and where we were as a movement or as a political/ideological point of view, that was pretty remarkable, to get 1 percent of the vote.”

Koch gave his own vice presidential campaign $100,000 a month after being chosen as Ed Clark’s running mate. “We’d like to abolish the Federal Elections Commission and all the limits on campaign spending anyway,” Koch said in 1980. When asked why he ran, he replied: “Lord knows I didn’t need a job, but I believe in what the Libertarians are saying. I suppose if they hadn’t come along, I could have been a big Republican from Wichita. But hell — everybody from Kansas is a Republican.”

From 1982 to 2013, Koch contributed $18.6 million to WGBH Educational Foundation, including $10 million to the Public Broadcasting Service (PBS) show Nova. Koch was a contributor to the Smithsonian Institution in Washington, D.C., including a $20 million gift to the American Museum of Natural History, creating the David H. Koch Dinosaur Wing and a contribution of $15 million to the National Museum of Natural History to create the new David H. Koch Hall of Human Origins, which opened on the museum’s 100th anniversary of its location on the National Mall on March 17, 2010. He also served on the executive board of the Institute of Human Origins. In 2012, Koch contributed US$35 million to the Smithsonian to build a new dinosaur exhibition hall at the National Museum of Natural History.

In 1984, Koch broke with the Libertarian Party when it supported eliminating all taxes. Subsequently, Koch was a Republican. Koch donated to various political campaigns, most of which were Republican. In February 2012, during the Wisconsin gubernatorial recall election, Koch said of Wisconsin governor Scott Walker, “We’re helping him, as we should. We’ve gotten pretty good at this over the years. We’ve spent a lot of money in Wisconsin. We’re going to spend more,” and said that by “we” he meant Americans for Prosperity.

Koch donated funds to various advocacy groups. In 1984, he founded Citizens for a Sound Economy (CSE). He served as its Chairman of the board of directors and donated funds to it. Richard H. Fink served as its first president. Koch was the chairman of the board and gave initial funding to the Americans for Prosperity Foundation and to a related advocacy organization, Americans for Prosperity. A Koch Industries spokesperson issued a press release stating “No funding has been provided by Koch companies, the Koch foundations, or Charles Koch or David Koch specifically to support the tea parties.” Koch was the top initial funder of the Americans for Prosperity Foundation at $850,000. Koch said that he sympathized with the Tea Party movement, but denied directly supporting it, having stated that: “I’ve never been to a tea party event. No one representing the tea party has ever even approached me.”

In February 1991, Koch was a passenger on board USAir Flight 1493 when it collided with another aircraft on a runway at Los Angeles International Airport, killing 35 people. Koch survived and said in an interview in 2014 that it helped change his life and prompted him to become “tremendously philanthropic”.

In 1992, Koch was diagnosed with prostate cancer. He underwent radiation, surgery, and hormone therapy, but the cancer repeatedly returned. Koch said he believed his experience with cancer encouraged him to fund medical research.

Following Jacqueline Kennedy Onassis’ death in 1994, Koch purchased her 15-room apartment at 1040 Fifth Avenue. In 1996 he married Julia Flesher; The apartment wasn’t roomy enough after the birth of their third child, so Koch sold it to billionaire Glenn Dubin in 2006 and moved with his family to 740 Park Avenue.

Koch said his biggest contributions go toward a “moon shot” campaign to finding the cure for cancer, according to his profile on Forbes. Between 1998 and 2012, Koch contributed at least $395 million to medical research causes and institutions.

Koch established the David H. Koch Charitable Foundation. Beginning in 2006, the Chronicle of Philanthropy listed Koch as one of the world’s top 50 philanthropists. He sat on the Board of Trustees of NewYork–Presbyterian Hospital from 1988 until his death in 2019.

In 2006, Koch gave $20 million to Johns Hopkins University School of Medicine in Baltimore for cancer research. The building he financed was named the David H. Koch Cancer Research Building.

In 2007, he contributed $100 million to the Massachusetts Institute of Technology for the construction of a new 350,000-square-foot (33,000 m) research and technology facility to serve as the home of the David H. Koch Institute for Integrative Cancer Research. From the time he joined the MIT Corporation in 1988, Koch gave at least $185 million to MIT, $15 million to NewYork–Presbyterian Hospital Weill Cornell Medical Center and $30 million to the Memorial Sloan Kettering Cancer Center in New York City. The same year, he donated $25 million to the University of Texas M. D. Anderson Cancer Center in Houston to establish the David Koch Center for Applied Research in Genitourinary Cancers.

In July 2008, Koch pledged $100 million over 10 years to renovate the New York State Theater in the Lincoln Center for the Performing Arts; the Theater is the home of the New York City Ballet. According to The New York Times, Koch’s gift was “transformative, enabling a full-scale renovation of the stage” that included “an enlarged orchestra pit that mechanically rises”. The theater was renamed the David H. Koch Theater. Koch also pledged $10 million to renovate fountains outside the Metropolitan Museum of Art.

As of 2010, David Koch owned 42 percent of Koch Industries, as did his brother Charles. He held four U.S patents. Koch served as an executive vice president of Koch Industries until retiring due to health issues in 2018. His retirement was announced on June 5, 2018.

In August 2010, Jane Mayer wrote an article in The New Yorker on the political spending of David and Charles Koch. It stated: “As their fortunes grew, Charles and David Koch became the primary underwriters of hard-line libertarian politics in America.” An opinion piece by journalist Yasha Levine in The New York Observer said Mayer’s article had failed to mention that the Kochs’ “free market philanthropy belies the immense profit they have made from corporate welfare.”

In 2011, 2014, and 2015 Time magazine included Charles and David Koch among the Time 100 of the year, for their involvement in supporting the Tea Party movement and the criticism they received from liberals.

In 2011 Koch gave $5 million to the House Ear Institute, in Los Angeles, to create a center for hearing restoration, and $25 million to the Hospital for Special Surgery in New York City In 2013, he gave $100 million to NewYork–Presbyterian Hospital, the largest philanthropic donation in its history, beginning a $2 billion campaign to conclude in 2019 for a new ambulatory care center and renovation the infrastructure of the hospital’s five sites.

In 2012, Koch spent over $100 million in a failed bid to oppose the re-election of President Barack Obama.

Koch opposed several of President Barack Obama’s policies. An article from the Weekly Standard, detailing the “left’s obsession” with the Koch brothers, quotes Koch stating that Obama is “the most radical president we’ve ever had as a nation … and has done more damage to the free enterprise system and long-term prosperity than any president we’ve ever had.” Koch said that Obama’s father’s economic socialism, practiced in Kenya, explains why Obama has “sort of antibusiness and anti-free enterprise” influences. Koch said that Obama is “scary”, a “hardcore socialist” who is “marvelous at pretending to be something other than that.” Koch contributed almost entirely to Republican candidates in 2012.

Koch was the fourth-richest person in the United States in 2012 and was the wealthiest resident of New York City in 2013. As of June 2019, Koch was ranked as the 11th-richest person in the world (tied with his brother Charles), with a fortune of $50.5 billion.

In July 2015, David and Charles Koch were commended by both President Obama and activist Anthony Van Jones for their bipartisan efforts to reform the prison system in the United States. For nearly 10 years, the Kochs advocated for several reforms within the criminal justice system which include reducing recidivism rates, simplifying the employment process for the rehabilitated, and defending private property from government seizures through asset forfeiture. Allying with groups such as the ACLU, the Center for American Progress, Families Against Mandatory Minimums, the Coalition for Public Safety, and the MacArthur Foundation, the Kochs maintained that current prison system unfairly targeted low-income and minority communities at the expense of the public budget.

In 2015, he committed $150 million to Memorial Sloan Kettering Cancer Center in New York City to build the David H. Koch Center for Cancer Care, which will be housed in a 23-story building in development between East 73rd and 74th Streets overlooking the FDR Drive. The center will combine state-of-the-art cancer treatment in an environment that supports patients, families, and caregivers. The building will include flexible personal and community spaces, educational offerings, and opportunities for physical exercise.

Koch died at his home in Southampton, New York, on August 23, 2019, at the age of 79. Koch’s wife, Julia Koch, and their three children inherited a 42% stake in Koch Industries from Koch upon his death.