Garr was born into a show business family: Her father was a vaudeville performer and her mother was a Rockette. After launching her own performing career as a dancer, she made her film debut with a tiny role in 1963's A Swingin' Affair. She went on to appear in a string of Elvis Presley films, including Fun in Acapulco (1963), Kissin' Cousins (1964), Viva Las Vegas (1964) and Clambake (1967). In the early 1970s, Garr was a regular on such TV shows as The Sonny and Cher Comedy Hour. Garr's big-screen breakthrough came in 1974, when she was featured in writer-director Francis Ford Coppola's The Conversation, a psychological thriller starring Gene Hackman as a surveillance expert. The film received three Academy Award nominations, including Best Picture. That same year, the blonde actress played Dr. Frankenstein's pretty lab assistant Inga in director Mel Brooks' hit horror spoof Young Frankenstein, which co-starred Gene Wilder, Peter Boyle, Marty Feldman, Madeline Kahn and Cloris Leachman.
In 1977, Garr co-starred in director Carl Reiner's Oh, God!, playing the skeptical wife of a supermarket manager (played by John Denver) who is picked by God (George Burns) to spread his message. In Steven Spielberg's multiple Oscar-nominated hit Close Encounters of the Third Kind later that year, Garr played another disapproving mate, this time of a cable guy (Richard Dreyfuss) who displays increasingly strange and obsessive behavior after an encounter with a UFO. In 1979, Garr appeared in The Black Stallion, based on the classic children's novel by Walter Farley.
In 1982, Garr co-starred in Tootsie, writer-director Sydney Pollack's comedy about an out-of-work actor, played by Dustin Hoffman, who dresses in drag to land a role. The film was a huge box-office success and earned nine Academy Award nominations, including Best Picture and Best Supporting Actress for Garr's portrayal of Sandy Lester, the neurotic actress friend of Hoffman's character. Garr lost the Oscar to her Tootsie cast mate, Jessica Lange, who played a soap actress for whom Hoffman's character falls.
Garr went on to appear in such films as Mr. Mom (1983), with Michael Keaton, After Hours (1985), Mom and Dad Save the World (1992) and Dumb & Dumber (1994). Known for her comedic talents, she's hosted Saturday Night Live several times and has been a frequent guest on The Late Show with David Letterman. Garr also appeared on the hit sitcom Friends as the estranged biological mother of Phoebe Buffay, played by Lisa Kudrow.
In 2002, Garr publicly announced that she has been suffering from multiple sclerosis for a number of years. Since then, she has been a dedicated advocate for awareness of the disease. Garr published an autobiography, Speedbumps, in 2005.