DeCamp first came to fame in November 1937, when she took the role of Judy Price, the secretary of Dr. Christian in the long-running radio series of the same name. She made her film debut in Cheers for Miss Bishop and appeared in many Warner Bros. films, including Eyes in the Night, Yankee Doodle Dandy playing Nellie Cohan opposite James Cagney, This Is The Army playing the wife of George Murphy and the mother of Ronald Reagan, Rhapsody in Blue and Nora Prentiss. She played the mother of the character played by Sabu Dastagir in Jungle Book.
DeCamp played Peg Riley in the first television version of The Life of Riley opposite Jackie Gleason in the 1949-1950 season, then reprised the role on radio with original star William Bendix for an episode of Lux Radio Theater in 1950. From 1955-1959 she was a regular on the popular NBC television comedy The Bob Cummings Show, playing Margaret MacDonald, widowed sister of Cummings's character, the womanizing photographer and former World War II pilot Bob Collins; Dwayne Hickman (the future star of The Many Loves of Dobie Gillis) portrayed her son, Chuck. DeCamp had a recurring role as Helen Marie, the mother of Marlo Thomas on That Girl, from 1966-1971 on ABC. She also appeared in several episodes of the CBS sitcom Petticoat Junction as Kate Bradley's sister, Helen, filling in as a temporary replacement for the ailing Bea Benaderet as the mother figure to Bradley's three daughters.
In 1962, she appeared as a dishonest Southern belle in the NBC sitcom Ensign O'Toole with Dean Jones. She appeared in the role of Gertrude Komack in the episode entitled "A Little Anger is a Good Thing" on ABC's medical drama Breaking Point.
Viewers in the 1960s also knew her from her many appearances in commercials for the laundry product 20 Mule Team Borax.
She also played the faithful nurse on the Dr. Christian radio show, starring Jean Hersholt, and she played Buck Rogers' mother in flashback scenes of the Buck Rogers in the 25th Century episode "The Guardians".
On 7 July 1946, her Beverly Hills home was damaged when a wing hit it after the experimental XF-11 piloted by Howard Hughes (re-created in the 2004 movie, The Aviator) crashed nearby. A piece of the wing and a part of the neighbor's roof landed in DeCamp's bedroom, where she and her husband were sleeping, with no injuries.
Outliving most of her contemporaries, DeCamp died of pneumonia in 2001. She was 90 years of age. She had four daughters: Margaret, Martha, Valerie and Nita.