Following her five-year run on Lassie, Lockhart made a guest appearance on Perry Mason as defendant Mona Stanton Harvey in "The Case of the Scandalous Sculptor".

Lockhart then starred as Dr. Maureen Robinson in Lost in Space, which ran from 1965 to 1968 on CBS, opposite veteran actors Guy Williams and Jonathan Harris.

In 1965, Lockhart played librarian Ina Coolbrith, first poet laureate of California, in the episode "Magic Locket" of the syndicated Western series Death Valley Days.

She then appeared as Dr. Janet Craig on the final two seasons of the CBS sitcom Petticoat Junction (1968–1970); her character was brought in to fill the void created after Bea Benaderet died during the run of the show.

In 1991, Lockhart appeared as Miss Wiltrout, Michelle Tanner's kindergarten teacher on the TV sitcom Full House.

In 2004, Lockhart voiced the role of Grandma Emma Fowler in Focus on the Family's The Last Chance Detectives audio cases.

In February 2013, Lockhart began filming for Tesla Effect, a video game that combines live-action footage with three-dimensional graphics, which was released in May 2014.

In 1948, Lockhart received a Special Tony Award for Outstanding Performance by a Newcomer (a category that no longer exists) for her role on Broadway in For Love or Money.

[8] Lockhart donated her Tony Award to the Smithsonian Institution in 2008 for display in the museum's permanent entertainment archives.

A Roman Catholic, Lockhart, along with her daughter Anne and actress Kay Lenz, met Pope John Paul II in 1985.

Her reporter friend Merriman Smith arranged for her to travel with both major-party candidates in the 1956 presidential election, Dwight D. Eisenhower and Adlai Stevenson.

In numerous interviews, her Lost in Space co-star Bill Mumy stated that she took him and Angela Cartwright to concerts at the Whisky a Go Go in Hollywood.