Leo McGarry is from Chicago, Illinois, though there seems to be some family connection to (likely one or more of his parents were born in) Boston, Massachusetts. He had at least two sisters, Elizabeth and Josephine, the latter serving as a school district superintendent. It is strongly suggested that McGarry earned either his undergraduate or law degree from the University of Michigan. McGarry is a recovering alcoholic and valium addict. Despite these addictions it was his workaholic attitude towards his job as Chief of Staff that contributed to his divorce during the first season from wife Jenny. McGarry is an Air Force veteran and has achieved the rank of colonel , having flown F-105 Thunderchief fighter-bombers in the Vietnam War. Prior to working in the White House, McGarry had been the Secretary of Labor during a presidency prior to the beginning of the show. He also speaks fluent Spanish. McGarry had amassed significant wealth during his life in the private sector as a member of the board of directors of a prominent defense company. A running joke on the show is that McGarry has the wealth necessary to bail out the government when funds are thin for new projects.

McGarry and ex-wife Jenny have a daughter, Mallory, who is a recurring character and was once a potential love interest for Sam Seaborn. Sam and Mallory spend most of their time arguing; Mallory usually picks the fights just to have Sam argue with her. After Sam left the White House, Mallory is largely absent from the show, although it was revealed she married and had a son.

Having resigned from his post as Secretary of Labor sometime in mid-1997, McGarry goes on to New Hampshire to persuade Governor Josiah Bartlet, an old friend, to run for the Democratic presidential nomination. Having so persuaded Bartlet, McGarry becomes his campaign manager and General Chairman of the "Bartlet For America" campaign, hiring such top political talent as Josh Lyman, Toby Ziegler, C.J. Cregg, and Sam Seaborn to work for the campaign. Eventually, Governor Bartlet, who was considered to be an insurgent candidate by the media, defeats Senator John Hoynes of Texas (whom Bartlet picks as his vice presidential nominee to balance the ticket) for the nomination and goes on to win the presidency.

As President Bartlet's top advisor, McGarry has an office adjacent to the Oval Office and sits in with the president in the Situation Room. McGarry is very involved in the formation of policy and the day-to-day operations of the White House and its staff. On more than one occasion, McGarry is said to be the man who "runs the country", and is treated with great respect by people on both sides of the aisle.

In season six, during a Middle East peace negotiation at Camp David, McGarry finds it impossible to support Bartlet's position, and (in a very tense moment) Bartlet and McGarry come to an agreement that McGarry would be resigning at the first available opportunity. Minutes after the conversation, McGarry suffered a heart attack and collapsed while walking alone on the grounds. He is resuscitated, survives, and later returns to work after Bartlet's last State of the Union Address in his new role as Senior Counselor to the President. McGarry is succeeded as Chief Of Staff by C.J. Cregg, up to this point, the White House Press Secretary.



However, Bartlet asks him to run the Democratic National Convention when it seems likely to deadlock. The Democratic Party's eventual presidential nominee, Congressman Matt Santos selects McGarry as his vice presidential nominee. This is particularly ironic, because McGarry had earlier repeatedly insisted that Santos drop out of the race for the sake of party unity.

During the ensuing campaign, the press and others tend to refer to McGarry as "Mr. McGarry" as opposed to "Secretary McGarry" as would be the standard protocol for a former cabinet member.

On Election Night, McGarry goes up to his hotel room in Houston to take a nap before the results come in. McGarry collapses in his hotel bathroom of an apparent heart attack. He is found by Annabeth Schott who rushes him to the hospital, where he is pronounced dead. McGarry's death comes ninety minutes before the polls close in California and other western states, thus giving some voters this information prior to casting their vote. Despite McGarry's death, the Santos-McGarry ticket narrowly wins the election over the Vinick-Sullivan ticket by a 30,000 vote margin in Nevada.



McGarry's funeral is held at an unnamed Catholic church, though the funeral was filmed at The Cathedral of Mary Our Queen in Baltimore, MD. President Josiah Bartlet, President-elect Matthew Santos, Josh Lyman, Charlie Young, former DNC head Barry Goodwin, and McGarry's unnamed son-in-law serving as pallbearers. He is buried at Arlington National Cemetery.