Damon grew up next door to historian and author Howard Zinn. Damon worked Zinn's popular book A People's History of the United States into his character's dialogue in the movie Good Will Hunting, saying: "That book will knock you on your ass." Later he did the narration for Zinn's own biographical film You Can't Be Neutral on a Moving Train and an audio version of A People's History of the United States.

He graduated from Cambridge Rindge and Latin School in 1988, the only public high school in Cambridge. He began Harvard University in the fall of 1988 and could have graduated with the class of 1992, but kept leaving classes to pursue acting projects, including the TNT original movie Rising Son and ensemble prep-school drama School Ties. While at Harvard, he concentrated in English and lived in Lowell House. He did not take part in student theatre generally, but did appear in A... My Name is Alice (in one of the three male roles usually performed by women). Damon dropped out of university to pursue his acting career in Los Angeles after Geronimo: An American Legend was expected (incorrectly) to be a big success.

Damon's first film role came in 1988 with one line in the romantic comedy Mystic Pizza. Damon appeared in small roles before landing a big part in Geronimo: An American Legend with Gene Hackman and Jason Patric. He next appeared as a heroin-addicted soldier in 1996's Courage Under Fire. He was required to lose 40 pounds (18 kg) in 100 days (for only two days of filming).After following a self-prescribed diet and fitness regimen to lose the weight, Damon was advised after the filming that he was fortunate his heart did not shrink. Damon was required to be on medication for several years to correct the stress inflicted on his adrenal gland, but maintains it was worthwhile to properly reflect his character's anguish and to show the industry how committed he was to the role.

Damon and actor Ben Affleck, close personal friends as well as co-stars in several films, developed a thriller about a young math genius, which they pitched around Hollywood. Receiving advice from writer/director/actor Rob Reiner, screenwriter William Goldman, and their friend writer/director Kevin Smith, the two changed the script around to focus on a young math genius trying to make his way in the world. Goldman's only advice was to agree with Reiner in that the script should lose its early thriller focus. This script eventually became Good Will Hunting, which earned both Damon and Affleck Oscars for Best Original Screenplay. Damon was also nominated for an Academy Award for Best Actor for the same film (which netted an Oscar for Best Supporting Actor for co-star Robin Williams). Damon parodied this as a fictional version of himself in Kevin Smith's Jay and Silent Bob Strike Back.

Damon founded Project Greenlight with Affleck and Chris Moore to find and fund worthwhile film projects from novice filmmakers. The televised documentary about the making of the film projects has been nominated for an Emmy three times.

Damon has been known to choose a wide variety of film roles, from his portrayal of bisexual murderer Tom Ripley in The Talented Mr. Ripley, for which he received a Golden Globe nomination for Best Actor, to a fallen angel who discusses pop culture as intellectual subject matter in Dogma, in which he co-starred with Affleck (1999); from a conjoined twin in Stuck on You, to a film he co-wrote with friend Casey Affleck and Gus Van Sant with limited dialogue--the low budget experimental film Gerry. Damon has been part of two major film franchises. He played amnesiac assassin Jason Bourne in the successful action movies The Bourne Identity and The Bourne Supremacy, with another Bourne sequel, The Bourne Ultimatum, released on August 3, 2007. He also starred as a youthful, optimistic thief Linus Caldwell opposite, among others, George Clooney, Brad Pitt, and Julia Roberts in Steven Soderbergh's remake of the Rat Pack's 1960 caper classic Ocean's Eleven, a frothy crime dramedy which was successful and has since spawned two sequels: Ocean's Twelve and Ocean's Thirteen, released on June 8, 2007.

Among other high profile roles, Damon played a fictionalized version of Wilhelm Grimm in Terry Gilliam's fantasy adventure The Brothers Grimm and an energy analyst in Syriana. He was recently onscreen in Robert DeNiro's The Good Shepherd as a career CIA agent, and played an undercover mobster working for the Massachusetts State Police in Martin Scorsese's Oscar-winning The Departed, a remake of the Hong Kong police thriller Infernal Affairs. He also has a supporting role in Kenneth Lonergan's film Margaret and an uncredited cameo in Francis Ford Coppola's Youth Without Youth, both due in 2007.

A Warner Brothers film has been in development that will have Damon and Steven Soderbergh working together again. The true story The Informant, when filmed at a future date, will have Matt Damon playing the role of Mark Whitacre, a corporate whistleblower. Whitacre wore a wire for two and a half years for the FBI as a high-level executive at a Fortune 500 company, Archer Daniels Midland (ADM), in one of the largest price-fixing cases in history. Filming is expected to commence on 15 April, 2008.

It has recently been rumored that producer J.J. Abrams is trying to get Damon to play James T. Kirk in the eleventh Star Trek feature film, which has been rumored to be either a prequel to, or a reboot of, the original Star Trek series. Damon told IGN on 20 July 2007 that he would not be in the film, as the director was casting significantly younger, and speculation about his casting had been solely based on Internet rumors.

On Wednesday, July 25, 2007, Damon became the 2,343rd person to receive a star on the Hollywood Walk of Fame.

Damon, along with frequent co-stars George Clooney and Brad Pitt, supports ONE, a campaign fighting AIDS and poverty in Third World countries. He has appeared in their print and television advertising.

Damon is a board member of GreenDimes.com, an organization that attempts to halt the tons of junk mail delivered to American homes each day. Appearing on The Oprah Winfrey Show on 20 April 2007, Damon promoted the organization's efforts to prevent the trees used for junk mail letters and envelopes from being chopped down. "For an estimated dime a day they can stop 70 per cent of the junk mail that comes to your house. It's very simple, easy to do, great gift to give, I've actually signed up my entire family. It was a gift given to me this past holiday season and I was so impressed that I'm now on the board of the company."

Damon is one of the founders of Not On Our Watch, an organization that focuses global attention and resources to stop and prevent mass atrocities such as in Darfur, along with George Clooney, Brad Pitt, Don Cheadle, and Jerry Weintraub. He is also the founder of H2O Africa, the charitable arm of the Running the Sahara expedition.

While filming Stuck on You in 2003, Damon met Argentine-born Luciana Bozan Barroso in Miami, where she was working as a bartender. They married in a private civil ceremony on December 9, 2005, in New York City Hall. Damon became stepfather to Barroso's young daughter, Alexia, from her previous marriage. The couple's first child together, daughter Isabella, was born on June 11, 2006.

Damon had a three-year relationship with Winona Ryder. He also dated Odessa Whitmire, who has worked as a personal assistant for Billy Bob Thornton and Ben Affleck, from 2001 to 2003. His relationship with Good Will Hunting co-star Minnie Driver reportedly ended when Damon announced their break-up on The Oprah Winfrey Show, though both actors have repeatedly denied this. Damon later stated that he was "sick and tired" of hearing the story, saying it was false. Driver's sister allegedly told Cosmo that the couple had broken up before the show was taped.

Damon, along with his best friend Ben Affleck, are die-hard Boston Red Sox fans.

Comedian Jimmy Kimmel often says: "Our apologies to Matt Damon, we ran out of time" near the end of his ABC television show Jimmy Kimmel Live, a gag lampooning instances where shows cannot feature their last guest due to time constraints. On September 12, 2006, after a segment highlighting the running gag and a lengthy introduction by Kimmel, Damon finally appeared on the show, only for Kimmel to apologetically cut his interview and head to credits. Damon told him "to go and fuck himself" and cursed Kimmel out during the credits. Kimmel later confirmed to USA Weekend that the skit was entirely planned and Damon willingly played along. Kimmel's girlfriend, comedian Sarah Silverman, also used this line at the end of the the 2007 MTV movie awards. This gag was also used again when Guillermo interviewed Matt at the Ocean's 13 premiere, with Damon asking "Are you with Kimmel?"

Damon appeared on Hardball with Chris Matthews in December 2006 and discussed the ongoing war in Iraq. Responding to Chris Matthews, Damon stated: "I don't think that it's fair, as I said before, that it seems like we have a fighting class in our country that's comprised of people who have to go for either financial reasons, or, I don't think that that is fair and if you're gonna send people to war ... then that needs to be shared by everybody."