The adopted daughter of director Cecil B. DeMille, she was considered Hollywood royalty and was noted for her dark beauty.

She signed a contract with Paramount Pictures and portrayed Princess Alice of France in her father's epic The Crusades (1935) and also starred in The Sky Parade (1936).

In his autobiography, her father wrote that she "has carried the name DeMille on for another generation in motion pictures as a talented actress.

[4] Her birth mother, Cecile Bianca Bertha Colani,[4] was of Italian descent and died in a Los Angeles hospital.

She played the second female role in All the King's Horses (1935) at Paramount, and was loaned to Columbia Pictures for The Black Room (1935) and to 20th Century Fox for Call of the Wild (1935).

Andre Sennwald of The New York Times wrote that the actors who gave "excellent performances" in the film included "that striking brunette, Katherine De Mille.

"[9] Paramount then cast her in two more leading roles; she was the sister of Buster Crabbe in the Western Drift Fence (1936) and a parachutist and the romantic interest of William Gargan in the aviation drama The Sky Parade (1936).

The studio cast her in the role of Margarita in its 1936 Technicolor film version of the Helen Hunt Jackson novel Ramona, starring Loretta Young as the title character.

She was Barbara Stanwyck's rival for the love of Joel McCrea in Banjo on My Knee (1936) and played the main female role in Charlie Chan at the Olympics (1937).

DeMille played supporting roles in the Roy Rogers vehicle In Old Caliente (1939), the RKO adventure Isle of Destiny (1940), the Columbia mystery film Ellery Queen, Master Detective (1940), the Universal mystery film Dark Streets of Cairo (1940), and Paramount's Technicolor adventure Aloma of the South Seas (1941).

After a six-year absence, DeMille returned to the screen when she co-starred with her husband, Anthony Quinn, for the first and only time in the Allied Artists drama Black Gold (1947), directed by Phil Karlson.

"[10] The Film Daily wrote: "Katherine DeMille does splendid work as Quinn's wife, who has had good schooling, but is a loyal, obedient helpmeet.

The Film Daily noticed that, as the Native American wife of the antagonist portrayed by Howard Da Silva, "Miss DeMille is properly sullen and tragic.