Born in Tulsa, Oklahoma, on June 10, 1963, Jeanne Tripplehorn became interested in performing through her father, guitarist Tom Tripplehorn, who recorded with the group Gary Lewis & The Playboys on such hits as "This Diamond Ring". Tripplehorn went to the University of Tulsa and New York's Julliard School of Drama.

Tripplehorn made her major TV debut in a supporting role in The Perfect Tribute in 1991. A year later she appeared in Basic Instinct, and then replaced a pregnant Robin Wright Penn in the role of Tom Cruise's wife in the box-office smash The Firm. Tripplehorn went on to work with Kevin Costner in the futuristic Waterworld, Gwyneth Paltrow in Sliding Doors, and Hugh Grant in Mickey Blue Eyes. Other film credits include Steal This Movie, Timecode, Paranoid, Relative Values, Dial 9 for Love, Swept Away, and The Moguls.