Jennifer Tilly was born Jennifer E. Chan in Harbor City, California. Her father was a Chinese stockbroker. Tilly is her mother's maiden name. Jennifer and her two sisters, Meg Tilly and Rebecca Tilly, were brought up in rural British Columbia, Canada. Jennifer began her acting career in her teenage years through a theatre program at Stephens Collage in Missouri.

Her breakthrough film role was as a singing waitress in The Fabulous Baker Boys (1989) in a part that was specially written for her by Steve Kloves. She was nominated for the Academy Award for Best Actress in a Supporting Role for her role as a hopelessly bad actress in Woody Allen's Bullets Over Broadway (1994).

Tilly gained some additional popularity in recent years for providing voice-over work as killer doll Tiffany for the Child's Play series of movies. In the most recent installment, Seed of Chucky, she plays a dual role, not only providing the voice for Tiffany, but also playing an exaggerated version of herself. She also played the wife of a murdered Italian Mafia son in Bella Mafia with Dennis Farina.

Tilly has also appeared in Bound, which revolves around a lesbian relationship her character has with Gina Gershon. In the movie, the two actresses engage in lesbian sex scene that is considered one of the most famous in the history of film. Gershon maintains that the orgasm she had in her scene with Tilly was authentic.

Tilly is a semi-regular cast member on Family Guy, voicing the Griffin family's neighbor, Bonnie. She has also done vocal work for the film Monsters, Inc., the children's series Hey Arnold, Stuart Little and The Haunted Mansion, where she does the voice over for Madame Leota and works from the neck up. She has been active in the theatre, winning a Theater World Award for her performance in the off-Broadway play One Shoe Off.

Jennifer Tilly has 3 new projects for 2006, The Poker Movie, The Funny Farm and a remake of The Initiation of Sarah for TV.

On June 27, 2005, Tilly won a World Series of Poker bracelet (and $158,625) in the Ladies' No-Limit Texas Hold 'Em event, outlasting 600 other players. This was especially astounding because it was not a celebrity open, and she is the first celebrity to win a World Series of Poker event. She followed up this accomplishment on September 1, 2005 by also winning the third World Poker Tour Ladies Invitational Tournament held at the Bicycle Casino in Los Angeles.

Tilly has also appeared in the Poker Royale series, and is currently appearing in the third season of Poker Superstars.

She also played in the Celebrity Poker Showdown which aired June 14th on Bravo. In the show Jennifer was knocked out in third place by Bravo¡¯s internet poker champion Ida Siconolfi (the first non-celebrity to appear on the show). Ida's starting hand was K¢À K¢¼, the second strongest hand in hold 'em. While Jennifer now short stacked moved all-in with the tenth strongest hand the A¢À K¢¾ , the flop came 3¢À J¢¼ 5¢À, the turn brought the 10¢¾, giving Jennifer extra outs by either getting an ace or a queen for the ace high straight but lost when the river showed a 7¢À , Ida later went on to win beating Fred Savage in heads-up.

Tilly married The Simpsons producer Sam Simon in 1984, but they divorced in 1991.

Tilly is currently dating poker professional Phil "Unabomber" Laak and is nicknamed "The Unabombshell" within the poker circuit.