She made her film debut in John Ford's The Long Voyage Home as a Cockney slattern, and portrayed the landlady in The Enchanted Cottage (1945).

Natwick is remembered for small but memorable roles in several John Ford film classics, including 3 Godfathers (1948), She Wore a Yellow Ribbon (1949), and The Quiet Man (1952).

[8] She was twice nominated for Tony Awards: in 1957 for The Waltz of the Toreadors, the same year she also starred in Tammy and the Bachelor with Debbie Reynolds and Leslie Nielsen[citation needed] and in 1972 for the musical 70 Girls 70.

[7] One of Natwick's memorable roles was in The House Without a Christmas Tree (1972), which starred Jason Robards and Lisa Lucas.

In 1971, Natwick co-starred with Helen Hayes in the ABC Movie of the Week, Do Not Fold, Spindle, or Mutilate, in which their characters worked together as amateur sleuths.

For her performance, Natwick won the Primetime Emmy Award for Outstanding Lead Actress in a Miniseries or a Movie.

[10] She guest-starred on such television series as McMillan & Wife, Family, Alice, The Love Boat, Hawaii Five-O, The Bob Newhart Show and Murder, She Wrote.