Henner was born in Chicago, Illinois, the daughter of Loretta Callis (born Nikoleta Kalogeropoulos), who died of arthritis at age 58 and Joseph Henner (whose surname was originally Pudlowski), who died of a heart attack at age 52. Her maternal grandparents were Greek and her paternal grandparents were Polish. Henner was raised on the northwest side of Chicago in the Logan Square neighborhood. She is the third of six children. Her mother was president of the National Association of Dance and Affiliated Arts and ran the Henner Dance School for 20 years. Henner took her first dance class at age two then went on to teaching dance at her family's studio when she was 14 and choreographed shows at local high schools and colleges until leaving the Chicago area during her third year of college.
While a student at the University of Chicago in the Hyde Park neighborhood of Chicago, Henner originated the role of "Marty" in the Kingston Mines production of Grease in 1971. When the show was discovered and moved to Broadway, she was asked to reprise the role; however, she chose instead to play "Marty" in the national touring company alongside John Travolta, who played "Doody". Additional Broadway credits for Henner include Over Here!, with Travolta, revivals of Pal Joey, Chicago, Social Security, and The Tale of the Allergist's Wife. Her first film appearance was in the 1977 sleeper-hit Between the Lines, co-starring then-unknowns Jeff Goldblum, Lindsay Crouse, John Heard, and Jill Eikenberry. Her second role was opposite Richard Gere in the 1978 film Bloodbrothers.
Henner came to prominence with the role of Elaine Nardo in the situation comedy Taxi. She was the leading lady in the 1982 film Hammett directed by Wim Wenders, produced by Francis Ford Coppola and starring her first husband Frederic Forrest. In 1983, Henner starred opposite Burt Reynolds in The Man Who Loved Women, directed by Blake Edwards. Reynolds then asked Henner to join the cast of Cannonball Run II later that year along with Shirley MacLaine and Dom DeLuise. She was the leading lady in the 1984 film Johnny Dangerously, playing love interest to Michael Keaton. In 1985 she once again appeared alongside John Travolta in Perfect. In 1991 she appeared opposite Steve Martin in L.A. Story as Trudi, a role for which she received a nomination for an American Comedy Award as the Funniest Supporting Female in a Motion Picture. From 1990 through 1994, she appeared opposite Burt Reynolds in the situation comedy Evening Shade, which also starred Ossie Davis and Hal Holbrook. She also appeared in Noises Off (1992) and in Man on the Moon (1999), a film about her Taxi co-star Andy Kaufman. Henner played herself (as well as herself playing her Taxi character).
Henner guested on Match Game and Hollywood Squares. She provided the voice for Gotham City socialite Veronica Vreeland in Batman: The Animated Series (1992–1999), reprising the role in the animated films Batman: Mask of the Phantasm (1993) and Batman & Mr. Freeze: SubZero (1998). In 1994, she hosted her own daytime talk show, Marilu, for 165 episodes.
Henner starred as the domineering mother of the bride in the Brooks & Dunn video "You Can't Take the Honky Tonk Out of the Girl" in 2003.
In 2006 and 2007, Henner was the host of the television series America's Ballroom Challenge. Henner said on an episode of The Ellen DeGeneres Show, in early 2008, that she has never actually danced ballroom and would like to go on a season of Dancing with the Stars. She later hosted FitTV and The Discovery Channel's Shape Up Your Life, which is based on her books.
Henner was a contestant on NBC's first The Celebrity Apprentice, in 2008. She was fired by Donald Trump in the eighth episode, but was brought back to help fellow contestant Trace Adkins in the final task of the show.
Henner, who has highly superior autobiographical memory, was a consultant for the CBS drama Unforgettable, which starred Poppy Montgomery as Carrie Wells, a woman with the same ability. Henner guest-starred as Carrie's aunt.
In August 2012, Henner won $25,000 for the charity Physicians Committee for Responsible Medicine (PCRM) as a celebrity contestant on Live! with Kelly "Grilling with the Stars" contest for her Healthy/Easy Grilled Mushroom and Heirloom Tomato dish.
Henner has written nine books on diet, health and memory, the most prominent being Total Health Makeover, in which she explains the virtues of a non-dairy diet in conjunction with food combining and exercise. She leads monthly classes on her website, www.marilu.com, designed to help people integrate these steps into a healthier, more active lifestyle. Both of her parents died in their 50s, which prompted her to lead a healthier lifestyle. Henner has also been host of television's The Art of Living, produced by United States Media Television.
Henner rejoined the cast for its 13th season on The All-Star Celebrity Apprentice where she is joined by fellow Apprentice alumni. She played for her charity The Alzheimer's Association and won over $50,000 for the cause. She returned, after being eliminated, for the final task to assist Trace Adkins.
Henner is now the host of The Marilu Henner Show. It airs every weekday morning on more than a dozen radio stations across America. The show is distributed by Sun Broadcast Group, in conjunction with GCN radio. The Marilu Henner Show can also be heard live at Marilushow.com, where she features guest physicians, health experts, celebrity guests and friends.
In her autobiography By All Means, Keep on Moving, Henner discussed her romances with actor John Travolta and Taxi costars Judd Hirsch and Tony Danza. Her first two marriages, to actor Frederic Forrest and director Robert Lieberman, ended in divorce. She married Michael Brown, a former college classmate, on December 21, 2006, before 100 people in her Los Angeles home. It was the second marriage for Brown, who has three children (Cassia Brown, Carine Brown and Michael Brown). Henner has two children, Nicholas Morgan and Joseph Marlon, from her marriage to Lieberman.
Henner has hyperthymesia and can remember the specific details of her everyday life since she was a small child. On December 19, 2010, CBS's 60 Minutes aired a segment which featured six individuals thought to have this condition. As a longtime friend of 60 Minutes correspondent Lesley Stahl, Henner was included on the show. She discussed her memory further on CBS' The Early Show, NBC's The Today Show, ABC's The View and Howard Stern's Sirius XM show. Her ninth book, Total Memory Makeover: Uncover Your Past, Take Charge of Your Future, is a New York Times best-seller and offers instruction on how people might access their own autobiographical memories; it was released on April 24, 2012. To promote Total Memory Makeover, she appeared on Anderson Live (then known as simply Anderson), The View, Piers Morgan Tonight, Good Morning America, CBS This Morning, The Talk, The Dr. Oz Show and numerous other radio and TV media outlets.Total Memory Makeover: Uncover Your Past, Take Charge of Your Future (April 24, 2012)Wear Your Life Well: Use What You Have To Get What You Want (April 8, 2008)Healthy Holidays (Oct 1, 2002)Healthy Kids: Help Them Eat Smart and Stay Active-For Life! (August 7, 2001)Healthy Life Kitchen (July 10, 2000)I Refuse To Raise A Brat (October 12, 1999)The 30-Day Total Health Makeover (March 3, 1999)Marilu Henner's Total Health Makeover (May 6, 1998)By All Means Keep Moving (September 5, 1994)