Tilton had early roles in television series such as Happy Days and Eight is Enough. She made her first film appearance alongside Jodie Foster in Freaky Friday. In 1978 Tilton made a cameo appearance in the John Milius film Big Wednesday. A year later, she made her big break by landing the role of Lucy Ewing, the sly, vixenish, frequently frustrated granddaughter of Jock Ewing in the popular television series Dallas from 1978 to 1985 and from 1988 to 1990. She also appeared on one episode of the show's spin-off series, Knots Landing, in 1980.
Tilton is also a singer; her own vocals were heard on a 1978 episode of Dallas. In 1984 she released a dance-pop single, "C'est La Vie", which became a hit in several countries in Europe, reaching #1 in Germany.
She appeared on Circus of the Stars in 1979 and 1991, on one occasion acting as a knife thrower's target girl in a gold bikini.
Tilton was the guest host on Saturday Night Live on February 21, 1981. The episode in question featured a parody of the famed "Who Shot J.R.?" episode of Dallas. In the episode, cast member Charles Rocket was shot in the chest by a sniper while doing a sketch about a sexy couple (with Gail Matthius as his partner) bathing a dog and spouting innuendo. At the end of the show, as cast members traditionally gathered around the host to say good night, Tilton asked Rocket how he felt about being shot. In character, a wheelchair-using Rocket improvised, "Oh, man, it’s the first time I've ever been shot in my life. I'd like to know who the fuck did it."
Tilton did a number of commercials in the 1990s for the Abdominizer workout equipment. She appeared as herself in an episode of Married... with Children where her involvement with the "Abdominizer" was spoofed. In addition, she has appeared in several spoof movies, such as The Silence of the Hams (1994), Superhero Movie (2008) and Paranormal Calamity (2010). In 2005 she appeared in the British reality TV show, The Farm.
In 2001, Tilton was honored by the Young Artist Foundation with its Former Child Star "Lifetime Achievement" Award for her role as Lucy Ewing on the original Dallas television series. She reprised her role as Lucy Ewing in TNT's Dallas revival series.
In January 2012 Tilton was a contestant on the British ice-skating show, Dancing on Ice, in its seventh season. She was paired with American figure skater, Matthew Gonzalez, who has previously worked with British actress, Daniella Westbrook. Tilton was voted out in week five of a twelve week run.