John Catsimatidis was born on the Greek island of Nisyros on September 7, 1948. He came to the United States with his parents when he was six months old.

The family moved to West Harlem, where Catsimatidis grew up. Catsimatidis' Father had been a lighthouse operator in Greece but worked as a busboy in New York. Catsimatidis graduated from Brooklyn Technical High School in 1966. He received a congressional nomination to West Point, but chose to study electrical engineering at New York University instead.

In 1971, Catsimatidis opened his first store, at Broadway and 99th Street. Shortly thereafter, he purchased another grocery store on 87th street just west of Broadway, naming it Red Apple. Among his Business innovations were staying open late seven days a week, offering free delivery, and cashing checks for customers. Catsimatidis has stated that by the time he was 24 years old, "I built up ten stores and the Business was doing $25 million a year, and I was personally earning a million dollars a year."

By the summer of 1981, Red Apple had 27 stores in the Bronx and Manhattan, with annual sales of around $40 million. These grew to $110 million in sales in 1985.

In 1986, Catsimatidis acquired United Refining Co., the owner of gasoline refineries in Pennsylvania and Alabama. In October 2009, Forbes Magazine reported that United Refining Energy Corp., a publicly traded special-purpose acquisition company (SPAC) sponsored by United Refining, was purchasing "privately held Chaparral Energy in a deal worth roughly $1.6 billion." However, United Refining Energy Corp. shareholders did not approve the deal and it was terminated in December 2009.

Catsimatidis is involved in philanthropy. He serves in a leadership role of the Greek Orthodox Archdiocese of America. He is one of the largest donors to the G&P Foundation for Cancer Research He founded and was co-chairman of Brooklyn Tech Endowment Foundation, benefiting his alma mater. Catsimatidis funds the John Catsimatidis Scholarship Fund at the New York University Stern School of Business, which has since 1988 awarded two scholarships each year. Catsimatidis was for five years President of the Manhattan Council of the Boy Scouts of America. He also served on the board of Directors of the Police Athletic League of New York City. Catsimatidis was also on the board of Directors of the Drum Major Institute.

On May 13, the New York Post ran a story on Catsimatidis' comment in a 1989 Crain's New York Business profile in which he stated "I'm a Manhattanite. I feel sorry for those people who aren't." Catsimatidis's remark was criticized by Republican Guy Molinari, the former Staten Island borough President and congressman, and Brooklyn Democratic councilman Lew Fidler, who called Catsimatidis a "Manhattan elitist."

Catsimatidis and his wife have made contributions to a variety of both Republican and Democratic campaigns. Among Republicans, the Catsimatidises contributed over $60,000 to the Republican National Committee, and have also made significant contributions to the National Republican Congressional Committee, National Republican Senatorial Committee, Mitt Romney, Eric Cantor, Olympia Snowe, richard Lugar, and others. Among Democrats handful of Democratic campaigns, including to Carolyn B. Maloney, Charlie Rangel, and Jerrold Nadler. In local New York City races, Catsimatidis has given to bill de Blasio (while he was a city councilman), Brooklyn Borough President Marty Markowitz, Cyrus Vance, Jr., and Staten Island Borough President James Molinaro. In the 1992 Democratic presidential primaries, Catsimatidis contributed $150,000 to the campaign of fellow Greek American Paul Tsongas.

Catsimatidis put on a fundraiser in 2006 with Michael Bloomberg for Senator Joe Lieberman of Connecticut to support his third party run as an independent after he lost the Democratic primary nomination for reelection to the Senate.

In 2008, Catsimatidis was widely viewed as a potential mayoral candidate, along with City Council Speaker Christine Quinn, Representative Anthony Weiner, businessman richard Parsons, Police Commissioner Raymond Kelly, City Comptroller bill Thompson (the eventual Democratic nominee), and state Senator Martin Golden. By July 2008, Catsimatidis formed an exploratory committee of advisors and operatives, including Robert Ryan, Alan Bernikow, Lawrence Mandelker, and Jose Ithier. McLaughlin & Associates was the committee's polling firm.

In 2009, Catsimatidis spent nearly $300,000, much of it on polls and consultants, to explore a candidacy. He said he only agreed to drop out after Bloomberg informed him of his plans to seek a third term. Once the city term limits law was changed to allow Bloomberg to run for a third term, Catsimatidis quietly withdrew. The exploratory committee was officially shut down in May 2009.

Catsimatidis and his wife have two children, Andrea and John Jr. Andrea graduated from New York University, and married Christopher Cox, grandson of former President richard Nixon, on June 4, 2011, at the Greek Orthodox Archdiocesan Cathedral of the Holy Trinity, "before a church packed with family members and political powerhouses," including Hillary Clinton, Henry Kissinger, Rudolph Giuliani, Charles Schumer, Ray Kelly, and Robert M. Morgenthau. An elaborate black-tie wedding reception for 700 guests was held at the Waldorf-Astoria. Catsimatidis stated that he spent "in excess of $1 million" on the wedding. Senator John McCain of Arizona was not invited, although Cox had worked on his 2008 presidential campaign, because McCain did not endorse Cox when he later ran (unsuccessfully) for Congress. Catsimatidis told the New York Post that "I thought that was low. I was just disgusted."

At campaign events in April, Catsimatidis claimed that he could have beaten Barack Obama in the 2012 presidential election and got into a contentious exchange with various Republican audience members, telling one to "go bullshit yourself if you want!" A spokesman for the Lhota campaign stated that "anyone running for mayor should be able to offer substantive ideas and solutions to our city's problems without engaging in irrational and antagonistic exchanges with voters."

Catsimatidis could have chosen to contest the general election on two other ballot lines (that of the Liberal Party of New York and another third-party line he created in summer 2013), but two days after his primary, he announced that he would withdraw from the race.

Among the "off-the-cuff—and off-beat—policy proposals" that Catsimatidis has suggested during the campaign include giving police tricycles to improve mobility, allowing casinos in hotels, and launching a program to give free pet food to people who adopt homeless animals. Catsimatidis's economic proposals include a revival of the 1964 New York World's Fair. The New York Times reported that Catsimatidis "struck an odd note when discussing education policy, expressing unease about the makeup of his daughter's graduating class from New York University's Stern School of Business," stating that "I think close to 480 of the 580 were Asian — Asian including India. And, it was scary. And then when you think about it, we’re going to deport most of these kids."

In the 2015 Forbes 400 "richest people in America" list, Catsimatidis ranked 182nd, with a personal net worth estimated at $3.4 billion; in the Forbes list of global billionaires, he ranked #577 Billionaires.