Cuomo attended New York City P.S. 50 and St. John’s Preparatory School. Cuomo was a baseball player, and while attending St. John’s University in 1952, he signed as an outfielder with the Pittsburgh Pirates organization for a $2,000 bonus, which he used to help purchase his wife Matilda’s engagement ring. Cuomo played for the Brunswick Pirates of the Class D Georgia–Florida League, where his teammates included future major leaguer Fred Green; Cuomo attained a .244 batting average, and played center field until he was struck in the back of the head by a pitch. Batting helmets were not yet required equipment, and Cuomo’s injury was severe enough that he was hospitalized for six days.

After his recovery, Cuomo gave up baseball and returned to St. John’s University, earning his bachelor’s degree summa cum laude in 1953. Deciding on a legal career, Cuomo attended St. John’s University School of Law, from which he graduated tied for first in his class in 1956. Cuomo clerked for Judge Adrian P. Burke of the New York Court of Appeals. Despite having been a top student, the ethnic prejudice of the time led to his rejection by more than 50 law firms before he was hired by a small but established office in Brooklyn. During his tenure at the law firm of Comer, Weisbrod, Froeb and Charles, Cuomo represented Fred Trump. Cuomo eventually became a partner at the firm, but stepped down in 1974 to become New York Secretary of State. In 1989, Cuomo settled a longstanding lawsuit against his former firm regarding $4 million in legal fees. In addition to practicing law, Cuomo worked as an adjunct professor at St. John’s University School of Law.

Cuomo first became widely known in New York City in the late 1960s when he represented “The Corona Fighting 69,” a group of 69 home-owners from the Queens neighborhood of Corona, who were threatened with displacement by the city’s plan to build a new high school. He later represented another Queens residents group, the Kew Gardens–Forest Hills Committee on Urban Scale, who opposed Samuel J. LeFrak’s housing proposal adjacent to Willow Lake in Queens. In 1972, Cuomo became known beyond New York City when Mayor John Lindsay appointed him to conduct an inquiry and mediate a dispute over low-income public housing slated for the upper-middle-class neighborhood of Forest Hills. Cuomo described his experience in that dispute in the book Forest Hills Diary, and the story was retold by sociologist Richard Sennett in The Fall of Public Man.

In 1974, he ran for Lieutenant Governor of New York on a ticket headed by gubernatorial candidate Howard J. Samuels, and both won the designation of the Democratic State Committee at the party convention. But their entire ticket, including the nominees for attorney general and U.S. Senator, was defeated in the Democratic primary election: Samuels by Rep. Hugh Carey of Brooklyn, and Cuomo by State Senator Mary Anne Krupsak.

In 1978, incumbent Lieutenant Governor Krupsak declined to seek re-election. She withdrew from the ticket and unsuccessfully challenged Carey in the gubernatorial primary, accusing him of incompetence. Cuomo won the primary for lieutenant governor and was elected alongside Carey in the general election.

In 1982, Carey declined to run for re-election and Cuomo declared his candidacy. He once again faced Ed Koch in the Democratic primary. This time, Koch’s support for the death penalty backfired and he alienated many voters from outside New York City when, in an interview with Playboy magazine, he described the lifestyle of both suburbia and upstate New York as “sterile” and lamented the thought of having to live in “the small town” of Albany as governor, saying it was “a city without a good Chinese restaurant”. Cuomo won the primary by ten points and faced Republican nominee businessman Lewis Lehrman in the general election. With the recession aiding Democratic candidates, Cuomo beat Lehrman 50.91% to 47.48%.

Cuomo established the Office of the MTA Inspector General (OIG) in 1983, as an independent watchdog for the Metropolitan Transportation Authority. The OIG provides oversight and monitors the activities of the MTA.

At its 1983 commencement ceremonies, Barnard College awarded Cuomo its highest honor, the Barnard Medal of Distinction. Also in 1983, Yeshiva University awarded him an honorary Doctor of Laws degree.

Cuomo actively campaigned for Walter Mondale in the 1984 presidential election, and was named on Mondale’s list of vice presidential candidates. Geraldine Ferraro was ultimately nominated as his running mate, but Cuomo was chosen to give the keynote speech at the 1984 Democratic National Convention in San Francisco. He vigorously attacked Ronald Reagan’s record and policies in his Tale of Two Cities speech that brought him to national attention, most memorably saying: “There is despair, Mr. President, in the faces that you don’t see, in the places that you don’t visit, in your shining city.” He was immediately considered one of the frontrunners for the Democratic nomination for president in 1988 and 1992.

Cuomo, a Roman Catholic, was personally opposed to abortion, but he was pro-choice on the issue, believing that the State does not have the right to ban it. In a speech at the University of Notre Dame on September 13, 1984, he used the statements of the American Catholic hierarchy to make an argument: “What is ideally desirable isn’t always feasible, … there can be different political approaches to abortion besides unyielding adherence to an absolute prohibition.” For this position, Cardinal John Joseph O’Connor considered excommunicating him.

Cuomo was the first guest on the long-running CNN talk show Larry King Live that began in 1985 and ended in 2010.

Cuomo was re-elected in 1986 against Republican nominee Andrew P. O’Rourke by 64.3% to 31.77%. He ruled out the possibility of running in the 1988 presidential election, announcing on February 19, 1987, that he would not run, and then going on to publicly decline draft movements in the wake of Gary Hart’s withdrawal following the Donna Rice affair.

Cuomo is also known for beginning the “Decade of the Child” initiative, an effort that included multiple health care and educational strategies to better the lives of children in New York State. Further, in 1988, the “Rebuild NY” Transportation Bond Act was an initiative under Cuomo that was a continuance of efforts to rebuild bridges and roads throughout the State. Cuomo increased assistance to local law enforcement agencies in order to help reduce or eliminate crime; and prison expansion in the State was continued which he is said to have regretted. Under Cuomo, New York State was also the first in the nation to enact seat belt laws.

Governor Mario and his wife Matilda Cuomo presided over the First New York State Family Support Conference in 1988. His statewide initiatives in developing over 1,000 family support programs are today termed “individual and family support” nationwide and are cited by the National Council on Disability. He was the first governor to support an ecological approach to families which was represented by community integration and community development as the goal of deinstitutionalization.

In the 1990 gubernatorial election, Cuomo was re-elected with 53.17% of the vote to Republican Pierre Andrew Rinfret’s 21.35% and Conservative Herbert London’s 20.40%.

Cuomo’s older son Andrew married Kerry Kennedy, a daughter of Robert F. and Ethel Skakel Kennedy, on June 9, 1990. They had three daughters, twins Cara Ethel and Mariah Matilda Cuomo, born on January 11, 1995; and Michaela Andrea Cuomo, born on August 26, 1997. The couple divorced in 2005. Andrew served as Secretary of Housing and Urban Development under President Bill Clinton from 1997 to 2001. In his first attempt to succeed his father, he ran as Democratic candidate for New York governor in 2002, but withdrew before the primary. He withdrew after criticizing Republican incumbent George Pataki’s leadership following the terrorist attacks on the city on September 11 the previous year. In November 2006, Andrew was elected New York State Attorney General; and on November 2, 2010, he was elected Governor of New York, inaugurated on January 1, 2011, and subsequently re-elected and sworn in on January 1, 2015, then re-elected again and sworn in to a third term on January 1, 2019.

The filing deadline for the New Hampshire primary was on December 20, 1991, and candidates were required to submit a ballot application in person. Cuomo was not able to negotiate a budget agreement with Republicans in the Legislature and on deadline day, time ran out. In a scene later fictionalized in Joe Klein’s Primary Colors, he kept an airplane idling on the tarmac as he pondered abandoning the budget talks in order to fly to New Hampshire and enter the race. Democratic party leaders asked him to run and he prepared two statements, one in case he ran and one in case he did not. He tried to come to a final agreement over the budget, but as he could not, he made an announcement at 3:30 p.m. that day:

When Cuomo was asked if he was planning to run for president in 1992, he said, “I have no plans and no plans to make plans,” but he refused to rule it out. In October 1991, news broke that he was interested in running and was taking advice from consultant Bob Shrum. At the same time, he began working on a budget with the New York State Legislature, and promised not to make any announcements about a presidential run until he had reached an agreement with the Republican-controlled State Senate and the Democratic-controlled State Assembly. Two polls taken in November of the New Hampshire Democratic primary showed him leading the field by at least twenty points, and a poll in December showed him trailing President George H. W. Bush 48% to 43%, having been behind by twenty-eight points two months earlier.

Cuomo’s supporters launched a draft movement and encouraged people to write in his name in the Democratic primary, which was held on February 18, 1992. Cuomo did not discourage it, which many saw as implicit endorsement of the campaign. Cuomo went on to receive 6,577 votes in the primary, 3.92% of the total cast and subsequently asked the draft committee to close down, saying, “I am flattered by their support and impressed by their commitment, but I am also convinced that in fairness to themselves they ought now to end their effort.” The group closed down, but Cuomo refused to rule out joining the primaries later in the year, stating, “I have said more than once that the nomination should go to someone willing and able to campaign for it. I am willing, but because New York’s budget has not been settled I am not able to campaign for it.” Ultimately, Cuomo did not enter the race and Bill Clinton went on to win the Democratic nomination and the general election. Because of Cuomo’s refusal to run for national office, despite his popularity, he was referred to as the “Hamlet on the Hudson”.

After Bill Clinton won the Democratic nomination for president in 1992, Cuomo was a candidate for vice president but he refused to be considered and did not make Clinton’s final shortlist. He was also spoken of as a candidate for nomination to the United States Supreme Court, but when President Clinton was considering nominees during his first term to replace the retiring Byron White, Cuomo stated he was not interested in the office. George Stephanopoulos wrote in 1999 that Clinton came within 15 minutes of nominating Cuomo before the latter pre-emptively rejected the post.

In 1994, Cuomo ran for a fourth term. In this election, Republicans attacked him for the weak economic recovery within the state since the early 1990s recession and the resulting high unemployment as well as his opposition to the death penalty by highlighting the case of Arthur Shawcross, a multiple murderer convicted of manslaughter who was paroled by the state in 1987 and while on release became a serial killer. Republicans were able to associate Shawcross with Cuomo much like Willie Horton with Michael Dukakis six years earlier. Cuomo was defeated by George Pataki in the 1994 Republican landslide, taking 45.4% of the vote to Pataki’s 48.8%. Cuomo lost mainly because his support outside of New York City all but vanished; he only carried one county outside the Five Boroughs, Albany County.

Cuomo was notable for his liberal political views, particularly his steadfast opposition to the death penalty, an opinion that was unpopular in New York during the high-crime era of the 1980s and early 1990s. While governor, he vetoed several bills that would have re-established capital punishment in New York State. The death penalty was reinstated by Governor Pataki the year after he defeated Cuomo in the 1994 election, although it was never put into effect and the statute was declared unconstitutional by the New York Court of Appeals in 2004.

Cuomo remained a baseball fan after his athletic career ended, reportedly limiting his television watching to baseball games and C-SPAN. He was an avid player of fantasy baseball, always with an Italian-American player on his team, regardless of how many Italian-American players were available or how well they were doing. In 1994, he was featured several times on the Ken Burns PBS series Baseball, where he shared memories of his life in baseball before he entered politics.

From 1995 until his death, Cuomo worked as counsel at the New York law firm, Willkie Farr & Gallagher. In 1996, Cuomo joined the board of Medallion Financial Corp., a lender to purchasers of taxi medallions in leading cities across the U.S. He was named to the board through his personal and business relationship with Andrew M. Murstein, president of Medallion. Cuomo also sat on the Advisory Council of the Abraham Lincoln Bicentennial Commission.

In 1996, Cuomo wrote Reason to Believe. He also wrote a narrative essay titled “Achieving the American Dream” about his parents’ struggles in coming to America and how they prospered. Cuomo was the author of Why Lincoln Matters, published in 2004, and he co-edited Lincoln on Democracy, an anthology of Abraham Lincoln’s speeches.

His daughter Margaret, is “a board certified radiologist, teaching professional, and national advocate for the prevention of cancer, heart disease, and diabetes”. She is the author of A World Without Cancer: The Making of a New World and the Real Promise of Prevention (2013), and she serves on the Board of Directors of the nonprofit organization, LessCancer. She has been featured on such TV shows as Good Morning America, Good Day New York, Morning Joe, and Inside Edition. In 2011, she was awarded the Commendation of the Order of the Star by the president and prime minister of Italy.

Cuomo’s younger son Chris was a journalist on the ABC Network news magazine Primetime. He anchored news segments and served as co-host on Good Morning America, before moving to CNN in 2013, where he co-hosted the morning news magazine New Day. He currently anchors his own prime time show Cuomo Prime Time. He was picked as one of People magazine’s 50 Most Beautiful People in 1997.

Cuomo was hospitalized for a heart condition and received treatment in November 2014. He was described as being “in good spirits” at that time. Cuomo died on January 1, 2015, at his home in Manhattan, New York, of heart failure, only hours after his son Andrew was sworn into a second term as Governor of New York State.

Cuomo was married for 60 years to Matilda (née Raffa), from 1954 until his death in 2015. She is a graduate of St. John’s University’s Teachers College. They had five children, Margaret, Andrew, Maria, Madeline, and Christopher. In 2017, Matilda was inducted into the National Women’s Hall of Fame.

Cuomo had a history of heart issues, which contributed to his death at the age of 82. His wake was held on January 5, 2015, and his funeral was held at Saint Ignatius Loyola Church in Manhattan on January 6. He is interred at St. John Cemetery, in Middle Village, Queens.

Maurizio Avola, a former Sicilian Mafioso believed to have killed about 80 people, including journalists, lawyers, politicians and mobsters, before becoming a pentito, or informer, and serving life in prison, told The Guardian in 2016 that the Sicilian Mafia had planned to assassinate Governor Cuomo on a visit to Italy in November 1992. The plan was for about a dozen gunmen armed with Kalashnikov assault rifles and explosives to ambush Cuomo. Avola’s godfather, Aldo Ercolano, considered that Cuomo would be an “excellent target”. Avola stated, “The aim was to target politicians or members of institutions in order to send out a clear message… Killing a prominent American was a warning to law enforcement agencies that had allowed several prominent mafia informants to live in the US under assumed identities.” This was several months after the mafia had already assassinated antimafia judges Giovanni Falcone and Paolo Borsellino. The attack was to be carried out in the main square of Messina, Sicily during the day. However, after Cuomo arrived in Rome on November 19 with security consisting of many bodyguards and a bulletproof car, the attack was called off.

In 2017, Governor Andrew Cuomo signed legislation officially naming the Tappan Zee Bridge replacement, the “Governor Mario M. Cuomo Bridge”.