Lewis dropped out of high school at 15 and subsequently passed the equivalency exam with the help of a tutor. She left school against the advice of her parents' friends, who, in contrast to her parents, suggested that she have a backup plan in case she didn't make it as an actress.

After leaving school, Lewis moved to Hollywood where she lived with friend Karen Black for a few months before moving into an apartment with one of her friends. She already had several roles to her credit, among them Mary Ash in the Showtime television series Home Fires and Kate Ferrell, the 13-year old daughter of widower/architect who marries his Central American housekeeper, an illegal alien, in the poorly received ABC sitcom I Married Dora. after appearing in the NBC pilot The Lisa Welchel Show she obtained a regular role in the short-lived NBC sitcom A Family for Joe, starring Robert Mitchum as a homeless man who is adopted by four orphans and appeared twice in the ABC sitcom The Wonder Years.

The first chance Lewis was given to demonstrate fully her ability was in the made for TV movie TOO YOUNG TO DIE? which was based on the true story of Amanda Sue Bradley, a sexually abused runaway teen who was the first minor to receive the death penalty.

Lewis' film career began as inauspiciously as had her first foray into TV. After paying a small part in Richard Benjamin's MY STEPMOTHER IS AN ALIEN, which starred Kim Basinger and Dan Akroyd, she appeared with her brother Lightfield in Tom Burman's MEET THE HOLLOWHEADS, the post nuclear story of a family living in underground tunnels.

Her next role was that of Audrey Griswold in NATIONAL LAMPOON'S CHRISTMAS VACATION. She portrayed yet another daughter in Michael Bortman's CROOKED HEARTS which featured Peter Coyote, Cindy Pickett as the parents of children played by Vincent D'Onofrio, Peter Berg, Noah Wyle, and Lewis.

Later in the same year, Lewis had her first screen credit as Danielle Bowden in Martin Scorcese's thriller CAPE FEAR for which she was nominated for both an Oscar and Golden Globe.
Lewis landed her biggest role to date in Oliver Stone's NATURAL BORN KILLERS.