Most moviegoers got their first look at Lewis in National Lampoon's Christmas Vacation (1989). But her range as an actress was showcased opposite Robert De Niro in Martin Scorsese's remake of Cape Fear (1991), earning her a Best Supporting Actress Oscar nomination. She followed the triumph with a string of high-profile performances in Husbands and Wives (1992), Kalifornia (1993), What's Eating Gilbert Grape (1993), Natural Born Killers (1994) and the vampire romp From Dusk Till Dawn (1996).
Balancing her time between acting and a singing career, Lewis continues to make her mark in films such as HBO's Hysterical Blindness (2002) and the comedies Old School (2003) and Starsky & Hutch (2004).