Procaccino was born in Bisaccia, Italy. When Mario was nine, the Procaccinos arrived in the United States, and despite poverty and discrimination, he graduated from City College and Fordham Law, becoming a lawyer in the 1930s. In the early 1940s, Mayor Fiorello La Guardia heard him address a war-bond rally and arranged for an appointment to a $3,500-a-year post in the city's legal department. When La Guardia's administration gave way to the Democrats, Procaccino became a party worker for Tammany Hall and was eventually given a minor judgeship. In 1965, the New York Democrats supported Procaccino, a candidate from the Bronx of Italian ethnicity for comptroller, along with a Jewish mayoral candidate, Abe Beame of Brooklyn, and an Irish-American from Queens, Frank O'Connor, for city council president. Procaccino and O'Connor were elected, but Beame was defeated by the Republican and Liberal Party of New York joint nominee, John Vliet Lindsay, a sitting member of the United States House of Representatives and a then ally of fellow New York liberal Republicans Governor Nelson A. Rockefeller and U.S. Senator Jacob K. Javits.
Procaccino's "fifteen minutes of fame" took place in 1969 when he won the Democratic primary for mayor with 32.8 percent of the vote in a five-man race, having defeated, among others, former Mayor Robert Wagner, Jr., liberal novelist Norman Mailer, and Bronx Borough President Herman Badillo, who later defected to the GOP. After briefly having a large lead in the general election race -- a June poll showed him leading Lindsay by fourteen points and getting his face on the major American newsmagazines, the mostly conservative Democrat lost ground quickly because he was unable to expand beyond his "law and order" platform. His campaign was, according to journalist Richard Reeves "the worst political campaign in American history." According to Reeves, Procaccino "snatched defeat from the jaws of victory."
Procaccino lost the mayoralty to Lindsay in this three-way race. The vote was split accordingly: Lindsay (Liberal) 42 percent, Procaccino (Democrat) 36 percent, and John Marchi (Republican), a member of the New York State Senate, 22 percent. For details, see New York City mayoralty elections#1969. Following the election, Procaccino worked as a Tax Commissioner for Governor Rockefeller and later returned to private practice.
However, his campaign had several lasting effects on national and New York politics. One was his characterization of his opponents as "limousine liberals", a term that has become a permanent part of American political discourse. The second effect was a change in New York City's election law. Because of Procaccino's slim plurality in the Democratic primary, if no candidate carries at least 40 percent of the vote, a runoff election must be held.
Procaccino was living outside the city in Harrison, NY, Westchester County, at the time of his death.