Born in Jamesport, Missouri, she became interested in acting in high school, and earned a degree from the University of Michigan before pursuing her acting dream. She got her start acting in shortened Shakespeare productions at the Century of Progress world's fair in Chicago, Illinois in 1933 - 1934.

Scott eventually went to New York City, where she was cast as the original Emily in the Broadway production of Our Town.

Her film debut in Our Town in 1940 saw her receiving an Academy Award nomination Best Actress for her luminous and critically acclaimed performance as Emily Webb.

She never again achieved such acclaim, although she appeared in such films as The Howards of Virginia, The Desperate Hours, The Ten Commandments, Ben-Hur, Airport 1975 and The Turning Point. In both The Ten Commandments and Ben-Hur, she played Charlton Heston's mother.

In 1968 she joined Henry Fonda and Robert Ryan in forming a theatrical production company called "The Plumstead Playhouse". It later became the Plumstead Theatre Company and moved to Los Angeles, California. The company produced such fare as First Monday in October, both on stage and on film (Walter Matthau and Jane Alexander appeared in the film). Scott co-produced both versions.

Her last production was Twelve Angry Men, which was performed at the Henry Fonda Theatre in Hollywood, California.

In the 1970s, she played Bob Newhart's mother on his eponymous CBS TV show.