O'Neill began auditioning for parts at age ten with her older siblings. After school, the kids would drive out to Hollywood. O'Neill made her first appearance on television at age 13 in an episode of Mama's Family as a younger version of Betty White's character, Ellen Harper. She continued working on television shows such as Matt Houston, Night Court, Highway to Heaven and The Twilight Zone. She also appeared on the American game show, Body Language in the summer of 1985. After an appearance on Family Ties, O'Neill won the role of the pregnant teenager Molly Stark on the daytime soap, The Young and the Restless for thirty episodes in 1986.

She appeared in the 1989 television films, Desperate for Love as Tammy Lauren's best friend, with Christian Slater and as Jodie in I Know My First Name is Steven, before appearing in her most recognized role as Amy Szalinski in Honey, I Shrunk the Kids. In the film, she and her brother are shrunk to 1/4 inch high by the father's (Rick Moranis) shrink ray. After the film, she was nominated for a Young Artist Award for Best Young Actress Supporting Role in a Motion Picture.

O'Neill continued work as Annette in an episode of Star Trek: The Next Generation, but most of her scenes were cut out due to time constraints. She can, however, be seen in the background of a crowd scene. She acted as Lisa Barnes in the pilot episode of Where's Rodney? with Honey co-star Jared Rushton and Rodney Dangerfield, but it wasn't picked up in 1990 or 1991. She continued working in television series such as Room for Romance, The Young Riders, and Gabriel's Fire.

After her interest in acting had waned, O'Neill quit acting in 1994 after getting scripts that required nudity. She met old childhood friend, Roy Johns, owner of a few circus acts. As she watched his work, she became interested in how active the girls in his performances were. She became involved with his acts and is now part of Johns' crew.

She is now part of the performance art community in Los Angeles. In 2002, she joined the Hollywood, Alabama trio, "Girls On Stilts." She has toured places in Italy and Asia, and has brandished her skills at Harrah's Casino, Disneyland, and other places. She doesn't have any children and is not currently married, but hoping to start a family with someone who isn't "intimidated" by her work as a performer.

O'Neill returned to television in 2005 to appear in an MTV documentary with her Honey, I Shrunk the Kids co-star Thomas Wilson Brown in The 100 Greatest Family Films. In 2008, she appeared as an Officer's wife in an independent film, The Japanese Sandman.