He graduated from the Phillips Academy in 1972 and graduated from the University of Pennsylvania in 1976.

While writing for The Philadelphia Inquirer he won the Pulitzer Prize for Investigative Reporting for his story on corruption in the Philadelphia court system in 1987.

In 1998 his article "Shattered Glass," an exposé of the career of New Republic writer Stephen Glass, was published in the magazine Vanity Fair, where he is a contributing editor. The article was later adapted for the 2003 film of the same name.

His magazine work has also appeared in the New York Times and Sports Illustrated. Bissinger's article for Vanity Fair, "Gone with the Wind" (August 2007) about the saga of 2006 Kentucky Derby Winner Barbaro, has been optioned by Universal Pictures. Bissinger's most recent article in Vanity Fair, "Inventing Ford Country" (March 2009) details the role Monument Valley played in the birth of American cinema.

In 2008, Bissinger wrote "The Throwback", an online sports column for the New York Times.

He is perhaps best known for his book Friday Night Lights, which documents the 1988 season of the football team of Permian High School in Odessa, Texas. This work went on to become a successful film, which was released in October 2004; and a television series which debuted on NBC on October 3, 2006. The book has sold nearly two million copies. In a list of the one hundred best books on sports ever, Sports Illustrated ranked Friday Night Lights fourth and the best ever on football. ESPN called Friday Night Lights the best book on sports over the past quarter-century.

He has written two books in addition to Friday Night Lights: A Prayer for the City (1998), which offers insight into the urban political scene of Philadelphia during Mayor (now Governor of Pennsylvania) Ed Rendell's term in the 1990s; and the New York Times' bestselling Three Nights in August (2005), which chronicles a series between the St. Louis Cardinals and the Chicago Cubs through the perspective of Cardinals manager Tony La Russa.

Bissinger has a self-professed "abiding hatred" for blogs and the "blog-o-sphere", and in April 2008 launched a tirade against sports blogger Will Leitch on a roundtable on Bob Costas's HBO series Costas Now.

Bissinger's newest book, Shooting Stars, was published by Penguin Press in September 2009. The book, co-authored with basketball superstar LeBron James, tells the story of James' high school career where he and his four best friends won a championship in basketball. As part of the promotion of Shooting Stars, Bissinger appeared as a "Guest Commenter" on a Deadspin post on Oct. 1, 2009.

Bissinger is married and has three sons. He divides his time between homes in Philadelphia and the Pacific Northwest.