McCormack was nominated for an Academy Award for Best Supporting Actress and a Golden Globe for Best Supporting Actress for The Bad Seed. On 20 March 1956, she received the Milky Way “Gold Star Award” as the most outstanding juvenile performer, in which Sal Mineo was placed third and Tommy Rettig second.

In 1957, she was cast by Orson Welles in his film adaptation of Don Quixote, but filming had to be abandoned for budgetary reasons, and was never fully completed. When a version was edited together in 1992, some years after Welles’ death, it did not include any of McCormack’s scenes, though they had been central to the framing of the plot. In 1959 she was in an episode of One Step Beyond called “Make Me Not a Witch”. She had the role of a pampered child star in the 1958 comedy Kathy O’ and recorded the title song for Dot Records. McCormack briefly starred in her own series, Peck’s Bad Girl, with Marsha Hunt and Wendell Corey in 1959, and had a leading role in MGM’s remake of The Adventures of Huckleberry Finn with Eddie Hodges. In the early 1960s, she starred in a series of popular teenage delinquent films, including The Explosive Generation with William Shatner and The Young Runaways. In 1962, she portrayed Julie Cannon in the Rawhide episode “Episode of the Wolves”; she appeared on the show again the following year, playing Sarah Higgins in the episode “Incident at Paradise”.

Her star on the Hollywood Walk of Fame is at 6312 Hollywood Boulevard. She received the star in 1960 aged 15, making her the youngest honoree on the Walk.

She married restaurateur Bob Catania in 1967, and the couple had two children before their marriage was dissolved. After a half-dozen teen roles during the 1960s, her film career gradually declined, but she continued to work in television. In 1970, she played Linda Warren on the soap opera The Best of Everything. She guest-starred on The Streets of San Francisco, season two, episode “Blockade”. She also portrayed a San Francisco paramedic on the season-seven Emergency! series episodes “What’s a Nice Girl Like You Doing…?” and “The Convention”. She resumed her cinema career with Bug in 1975.

McCormack held several recurring roles in popular television series, including Dallas, Murder, She Wrote, and The Sopranos. McCormack also starred as Anne Brookes, the wife of Jeffrey P. Brookes III (played by Jeffrey Tambor on the ABC television series The Ropers, a spin-off of Three’s Company starring Norman Fell and Audra Lindley, from 1979-1980. When Kathryn Hays left the CBS soap opera As the World Turns for an extended period, McCormack took Hays’ role until she returned. She starred as a psychotic mother in the cult thriller Mommy and its 1997 sequel Mommy 2: Mommy’s Day. In 2008, McCormack played First Lady Pat Nixon in the feature film Frost/Nixon. McCormack continues to work regularly and she costarred in the 2012 series Have You Met Miss Jones?. A recent film appearance is in the 2014 release Chicanery and she guest-starred in a 2013 episode of the series Hart of Dixie. Her most notable recent work was in the Paul Thomas Anderson film The Master.

In April 2018, it was announced that McCormack would join the cast of General Hospital temporarily replacing Leslie Charleson in the role of Monica Quartermaine due to injuries Charleson sustained in a fall. In September 2018, McCormack portrayed Dr. March, the child psychiatrist consulted in the 2018 television remake of The Bad Seed.