Jenney was born in Long Island City, Queens, New York. She began her acting career in 1979 with the film, Impostors. Several roles followed throughout the eighties, with appearances in the 1986 comedy The Whoopee Boys, and the award-winning Peggy Sue Got Married, with Kathleen Turner and Nicolas Cage. She appeared as 'Iris' in the Oscar-winning film Rain Man, starring Dustin Hoffman and Tom Cruise. In 1991, Jenney played waitress 'Lena' in Ridley Scott's Thelma & Louise; the following year, she appeared in American Heart, a film which earned her an Independent Spirit Award for Best Supporting Female. Jenney played the role of 'Anne Loomis' in the Joe Dante comedy Matinee, with John Goodman and Cathy Moriarty. During the nineties, she appeared in much smaller roles including Mr. Jones with Richard Gere, and Leaving Las Vegas, with Nicolas Cage and Elisabeth Shue, as well as Grace of My Heart. In 1997, she had a supporting role in the Tom Holland's horror film Thinner, which was based on the book by Stephen King. She also starred as medical officer Lieutenant Blondell in G.I. Jane, with Demi Moore, Mad City, with Dustin Hoffman and John Travolta, Desert Blue, with Kate Hudson and Christina Ricci, Practical Magic, with Sandra Bullock and Nicole Kidman and The Deep End of the Ocean, which starred Michelle Pfeiffer and was based on the book by Jacquelyn Mitchard. In 2000, Jenney portrayed Helen O'Donnell in Thirteen Days. She then appeared in romantic drama Crazy/Beautiful, with Kirsten Dunst and The Mothman Prophecies, starring Richard Gere. Jenney's has appeared in other roles in S.W.A.T., American Violet and Rogue River. In 2009, she made a cameo appearance in, The Hangover.