Fitzgerald was born to Irish immigrant parents in New York City. He paid for his university studies by working as a janitor and—like his father—as a doorman in Manhattan. Fitzgerald studied mathematics and economics at Amherst (Mass.) College, graduating in 1982. He earned a law degree from Harvard University in 1985 and worked in private practice until 1988, when he joined the U.S. Department of Justice (Southern District of New York) as an assistant U.S. attorney in New York City. In that job, he pursued cases against drug dealers, Mafia leaders, and terrorists—including the indictment of Osama bin Laden (bin Laden, Osama) in 1998 for the bombings of U.S. embassies in Kenya and Tanzania. He also developed a reputation for using obscure or long-forgotten laws to clinch a case; he built his case against Sheikh Omar Abdel Rahman (convicted for the 1993 World Trade Center bombing) upon a statute that dated back to the Civil War.

Despite a portfolio brimming with high-stakes, politically charged cases, Fitzgerald shunned affiliation with any political party—a stance that lent credence to his work. This helped when in 2001 Fitzgerald became the U.S. attorney in Chicago, where he brought corruption charges against Republicans and Democrats alike, among them former Illinois governor George Ryan and associates of Chicago Mayor Richard M. Daley (Daley, Richard M.). He again drew on the finer points of law, using mail fraud charges to bring indictments against Ryan.

Fitzgerald continued his work as the U.S. attorney in Chicago after becoming in 2003 the Justice Department's special prosecutor for the investigation into the leak of the identity of a covert Central Intelligence Agency officer (Valerie Plame). In October 2005, after two years of conducting interviews and collecting evidence, Fitzgerald indicted I. Lewis (“Scooter”) Libby, chief of staff to U.S. Vice Pres. Dick Cheney (Cheney, Dick), for having made false statements and having committed perjury during a grand jury investigation of the case. The following month Fitzgerald made new headlines by indicting Canadian-British media tycoon Conrad Black (Black, Conrad) for fraud. Both Libby and Black were later convicted. In December 2008 Fitzgerald filed criminal corruption charges against Illinois Gov. Rod Blagojevich, alleging that, among other things, Blagojevich had attempted to “sell” the U.S. Senate seat vacated by President-elect Barack Obama (Obama, Barack).