During the 1970s, McCall served as a State Senator representing Harlem and other parts of Manhattan. He left the Senate to accept an appointment from President Jimmy Carter as a member of the U.S. delegation to the United Nations with the rank of Ambassador.
In 1982 he was an unsuccessful candidate for the Democratic nomination for Lieutenant Governor of New York running on a ticket with Mario Cuomo. Cuomo later appointed McCall to serve as the state's Commissioner of Human Rights.
While serving in the private sector as a vice president with Citicorp, McCall accepted an appointment to the New York City Board of Education, where he served as President of the Board.
In 1993, McCall was elected by the New York State Legislature to fill the unexpired term of Republican Edward Regan as state comptroller. As comptroller, McCall was responsible for serving as the state's chief fiscal officer, conducting audits of state and local entities, signing state checks, being the state's bookkeeper, and serving as the sole trustee of the state pension fund.
He was elected state comptroller in 1994 defeating conservative Herbert London and in 1998 defeating Republican Bruce Blakeman. In 1998 he announced that he would not seek election to the U.S. Senate in 2000, leading in part to the successful candidacy of Hillary Rodham Clinton.
In 2002 McCall officially announced his campaign against Republican incumbent George Pataki. After his primary opponent, former housing secretary Andrew Cuomo, withdrew from the race, McCall entered the general election as the uncontested Democratic candidate, but lost to Pataki.
McCall was the favorite of the Democratic establishment but he faced a tough challenge from Cuomo which almost split the party. Cuomo proved to be a better fundraiser and McCall's own campaign war chest was heavily depleted in the primary battle. Although McCall did not make any negative attacks, his close supporter Charles B. Rangel stated that the McCall camp would not necessarily endorse Cuomo in the general election should the latter win. This backfired as some Italian Americans interpreted that as racism, while many of Cuomo's supporters refused to unite after McCall won the nomination.
Money would prove to be a handicap in the general election, as DNC Chairman Terry McAuliffe stated that he would not channel large sums of money to McCall's campaign unless the gap could be closed with Pataki, which McCall never managed to do.
Some of the letters referred to the size of the state's ownership interest in the corporation targeted, which critics claimed amounted to a veiled threat to punish companies that didn't hire his relatives. A Quinnipiac poll released October 16 showed that two-thirds of likely voters were aware of the letters and of those more than a fifth were less likely to vote for McCall as a result.
McCall defended the letters. Although he did issue a statement regretting the "appearance" and "impression" of the letters he wrote on government stationery, he maintained that he "never sought to leverage my public position nor mix my government role with my personal and professional relationship" in the letters.
Other political commentators attribute McCall's defeat to the growing popularity of the Republican Party after the terrorist attacks of September 11, 2001 along with Governor Pataki's successful administration of the state.
Tom Golisano was running in the general election as the Independence Party candidate and he also drew significant support away from McCall. At one point, McCall softened his attacks on Golisano in hopes of getting the latter to withdraw but that did not occur.
McCall was a member of the Board of the New York Stock Exchange from 1999 to 2003. Currently, he is a member of the Fiscal Control Board for Buffalo, New York. He also serves on the Boards of Directors for TYCO International, New Plan Realty, and TAG Entertainment Corporation, and as Chair of the New York State Public Higher Education Conference Board. An ordained minister, he spoke at Dartmouth College's annual Martin Luther King, Jr. Day celebration on January 15, 2006 about modern civil rights and the legacy of Dr. King. He operates his own fund called Convent Capital.
In January 2007, McCall was appointed to a panel, along with former New York State Comptroller Ned Regan and former New York City Comptroller Harrison Jay Goldin, to interview and recommend up to five candidates to the State Legislature to replace Alan Hevesi, who resigned due to scandal.
McCall is the recipient of twelve honorary degrees. In 2003, he was awarded the Nelson Rockefeller Distinguished Public Service Award from the Rockefeller College of Public Affairs and Policy at the University of Albany.