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Callie Khouri sparked nationwide debate in 1991 with the hit movie Thelma & Louise, her screenwriting debut, for which she won an Oscar for Best Original Screenplay. Khouri's script was also honored with a Writers Guild of America prize, a Golden Globe and a PEN Literary Award. Thelma & Louise took home the London Film Critics Circle Award for Film of the Year and was nominated for Best Original Screenplay by the British Academy of Film and Television Arts. In 1992, Khouri was the recipient of the second annual Los Angeles Women Making History Award and the New York Women in Communications Matrix Award. Glamour Magazine named her one of their Top Ten Women of the Year.

Khouri's second film as a screenwriter was Something to Talk About (1995), starring Julia Roberts, Dennis Quaid, Gena Rowlands, Robert Duvall and Kyra Sedgwick. She made her directorial debut with Divine Secrets of the Ya-Ya Sisterhood (2002), which Khouri also adapted for the screen. The film, starring Sandra Bullock, Ashley Judd, Ellen Burstyn and James Garner, grossed more than $70 million in the U.S. alone.

Serving on the WGA board of directors from 1996-1998 and 2000-2002, Khouri also sat on the board of trustees of the Writer's Guild Foundation from 2001 to 2004.

Khouri was awarded the 2005 Horton Foote Award for special achievement in screenwriting. In 2006, the filmmaker collaborated with legendary television producer Steven Bochco to create an original television series called Hollis and Rae. She wrote and directed the pilot.

Khouri was born in Texas and raised in Kentucky. She attended Purdue University, where she majored in drama, and pursued additional training at the Lee Strasberg Institute in Los Angeles as well as with Peggy Fuery. In 1985, Khouri began working in film production, producing commercials and music videos. She currently resides in the Los Angeles area.