Fraser was born in Indianapolis, Indiana, the son of Canadians Carol Mary (née Genereux) and Peter Fraser. His mother was a sales counselor, and his father was a former journalist who worked as a Canadian foreign service officer for the Government Office of Tourism. His maternal uncle, George Genereux, was the only Canadian to win a gold medal in the 1952 Summer Olympics, at the Olympic Trap. He has three older brothers: Kevin, Regan, and Sean. He has Irish, Scottish, German, Czech, and French-Canadian ancestry.
Fraser's family moved often during his childhood, living in Eureka, California; Seattle, Washington; Ottawa, Ontario; the Netherlands; and Switzerland. He attended Upper Canada College, a private boarding school in Toronto. While on vacation in London, he attended his first professional theatre show in the West End.
He graduated from Seattle's Cornish College of the Arts in 1990. He began acting at a small acting college in New York City. He planned on attending graduate school in Texas, but stopped in Hollywood on the way and decided to stay there to work in film.
Fraser made a brief appearance in the reenactment of America's Most Wanted, as a friend of murder victim Rodney Mark Peterson. Fraser got his first leading film role in the 1992 film Encino Man which was a moderate box office success and is considered a cult film.. That same year he starred with Matt Damon and Chris O'Donnell in School Ties. In 1994, he played Steve Nebraska in The Scout and Montgomery "Monty" Kessler in With Honors. He went on to star in films such as Philip Ridley's The Passion of Darkly Noon (1995) and The Twilight of the Golds (1997). He had his first major box office success with the 1997 film George of the Jungle which was based on the character created by Jay Ward. He went on to appear in several films which underperformed at the box office, such as Dudley Do-Right (1999) which was based on another Jay Ward character, Bedazzled (2000) and Monkeybone (2001).
He also played a dramatic role in 1998's Gods and Monsters, which was based on the life of James Whale (Ian McKellen) who directed Frankenstein. The film was written and directed by Bill Condon, and follows the loss of creativity, ambiguous sexuality and unlikely bonds between a heterosexual gardener and a homosexual, tortured and ailing filmmaker. His biggest commercial success came with the adventure fantasy film, The Mummy (1999) and its sequel The Mummy Returns (2001). He lent his voice for the unreleased animated film Big Bug Man. In 2004, he appeared in the Academy Award-winning film Crash.
He has also made guest appearances on the television shows, Scrubs, King of the Hill and The Simpsons. In March 2006, he was inducted into Canada's Walk of Fame, the first American-born actor to receive the honor. However, as of 2014, he does not have a star on the Hollywood Walk of Fame. After a six-year hiatus in the franchise, Fraser returned for the second sequel to The Mummy released in August 2008 and titled The Mummy: Tomb of the Dragon Emperor. Filming started in Montreal on July 27, 2007 and also starred Jet Li as Emperor Han. His other releases in 2008 were the 3D film adaptation of Jules Verne's Journey to the Center of the Earth and the fantasy film Inkheart (chosen personally for the lead role by the novel's author Cornelia Funke). In 2010, he starred in the drama film Extraordinary Measures with Harrison Ford.
Fraser starred as "Brick" in the West End production of Tennessee Williams's Cat on a Hot Tin Roof in September 2001, directed by Anthony Page. Castmates included Ned Beatty, Frances O'Connor and Gemma Jones. The show closed on January 12, 2002, with Fraser garnering many excellent reviews. In 2010, Fraser starred in a Broadway production of Elling, but the play closed after 9 performances due to lackluster reviews. After appearing in the critically panned Furry Vengeance in 2010, Fraser moved from being represented by William Morris Endeavor to the Creative Artists Agency. In 2010, he starred in Whole Lotta Sole directed by Terry George and in 2011, he was set to play William Tell in The Legend of William Tell: 3D, directed by Eric Brevig, with whom Fraser had also worked on in Journey to the Center of the Earth. Filming was delayed and late in 2011, Fraser sued the producer Todd Moyer for promised wages. Moyer later countersued for assault, which Fraser dismissed as a desperate attempt to avoid paying his debt. The film is currently in development limbo.
In 2016, Fraser replaced Ray Liotta in the upcoming Bollywood thriller, The Field.
Brendan Fraser later joined the recurring cast of The Affair during season 3 where he portrayed the misery-minded prison guard Gunther.
After arriving in Los Angeles, California, Fraser met actress Afton Smith while attending a barbecue at Winona Ryder's house on July 4, 1993. They married on September 27, 1998, and had three sons: Griffin Arthur Fraser (born 2002), Holden Fletcher Fraser (born 2004), and Leland Francis Fraser (born 2006). After their home in Beverly Hills, California sold in April 2007 for $3 million, Fraser's publicist announced in December 2007 that the couple had decided to divorce. In early 2013, Fraser petitioned the courts for a reduction of his alimony and child support payments, asserting that he was unable to meet the annual obligation of $900,000; Smith, in turn, accused Fraser of hiding financial assets.
Fraser speaks fluent French, and serves on the board of directors for FilmAid International. He is an accomplished amateur photographer, and has used several Instant cameras in movies and on TV shows, most notably on his guest roles on Scrubs. In his first appearance he used a Polaroid pack film; and on his second appearance he used a Holga with a Polaroid back, a Japanese-only model. The book Collector's Guide to Instant Cameras has a dedication to Fraser.