Wagner earned her BA at Carnegie Mellon University School of Drama in Pittsburgh, Pennsylvania. She began her career as an actress, appearing in several Broadway and off-Broadway stage productions. Wagner also performed at the Yale Repertory Theatre. In addition to being an actress, she is also a published playwright, co-writing the play Out of Our Father's House.

Wagner became a talent agent at the Creative Artists Agency; her clients included Kevin Bacon, Val Kilmer, Demi Moore, Liam Neeson, Oliver Stone, and Tom Cruise. Wagner paired Stone with Cruise for Born on the Fourth of July, with Kilmer on The Doors, and helped him cast JFK.

Cruise and Wagner formed Cruise/Wagner Productions in 1993. Their films include the Mission: Impossible series, Vanilla Sky, The Last Samurai, and War of the Worlds. Other projects include Without Limits, The Others, Narc, Ask the Dust, and Elizabethtown.

On November 2, 2006, MGM announced that Wagner and Cruise acquired a small stake in United Artists. Wagner was named CEO, while Cruise will serve as a producer. The announcement came after Sumner Redstone terminated Cruise's association with Paramount Pictures, citing that his personal life, religious beliefs, and controversial comments were a liability to the box-office earnings of Mission: Impossible III and the studio as a whole.

Wagner is married to Tom Cruise's agent Rick Nicita, who is also Co-Chairman of Creative Artists Agency.

She was a juror at the 2006 Venice Film Festival.