She made her acting debut in the ABC Afterschool Special Amy and the Angel, aired in 1982, alongside James Earl Jones, Meg Ryan, and Matthew Modine. This was also the only film she appeared in as a brunette. In 1984, she was cast as the title character, versus Faye Dunaway as Selena, in the film Supergirl, released in 1984. In her next film, she was cast alongside Christian Slater and Yeardley Smith as Billie Jean Davy, a modern day Joan of Arc, in the film The Legend of Billie Jean (1985). Next she appeared in two high profile comedies, Ruthless People (1986) and The Secret of My Succe$s (1987), playing ingenues in both roles. She also became a spokeswoman for Preference by L'Oral in both television and print ads.
Since the late 1980s, she has worked infrequently in television and film. She made a brief guest appearance on Seinfeld as a love interest of Jerry Seinfeld, who in reality is a huge fan of the Superman universe. More recently, Slater was seen in a recurring role as Clark Kent's biological mother, Lara, on the Superman-themed TV series Smallville.
In 2009, she guest starred in an episode of The CW horror series Supernatural.