As Bart Simpson on the Fox animated comedy "The Simpsons" (1990- ) and before that in shorts on "The Tracey Ullman Show" (Fox, 1987-90), her work was well known, although as a voice actor she was largely unrecognized in person. From childhood, Cartwright realized she had unusual vocal talents, and after a job at an Ohio radio station afforded her an opportunity to use her skills and get them noticed, it was advised that she get involved in animation. One of the contacts recommended to her was the legendary voice actor Daws Butler, who had brought life to Elroy Jetson, among other classic cartoon characters. Her ambition putting her into immediate action, Cartwright called Butler, and transferred to UCLA to be closer to his Beverly Hills home, where she was trained by him in vocal technique. Together they produced her demo reel, which got her work on the ABC Saturday morning animated series "The Richie Rich Show" (1980-82), voicing Richie's girlfriend Gloria. From there, many other animated voices would follow, with roles on several series including "Snorks" (NBC, 1984-86), "Galaxy High School" (CBS, 1986-88) and Pound Puppies (ABC 1986). Her voice could also be heard in the animated features "My Little Pony" (1986), "The Chipmunk Adventure" (1987), "Little Nemo: Adventures in Slumberland" (1990) and Disney's "The Little Mermaid" (1989).

While well known for her voice-over work, Cartwright also appeared in the flesh in several projects. Due to the youthful appearance of the blonde actress, early in her career she often played characters much younger than her real age. She made her film debut (playing a young girl) in the "It's A Good Life" segment of 1983's "Twilight Zone the Movie". Another notable role came two years later in the historical adventure "Flesh + Blood" (1985) starring Jennifer Jason Leigh. In 1998, she returned to the big screen with a small role as a secretary in "Godzilla". More prolific was Cartwright's small screen work, with appearance in several TV-movies and as a guest star on a number of series. In 1982, she made her debut in the title role of a young girl wrongly institutionalized in the CBS TV biopic "Marian Rose White". While she was cast primarily for her look, Cartwright handled the role more than capably. She followed up with a steady stream of telefilms while also continuing her plentiful voice work.

In 1987, a new chapter began in Cartwright's professional career when she was tapped to provide the voice of perennial ten-year old Bart Simpson, a sharp tongued mischief maker for animated segments of "The Tracey Ullman Show". From shorts on the show to its own long-running series on Fox, "The Simpsons" kept Cartwright in the public ear if not the public eye.