Born in Shoshoni, Fremont County, Wyoming, Jewell was a Broadway actress who achieved immediate success and glowing critical reviews in two productions, Up Pops the Devil (1930) and Blessed Event (1932).

She was brought to Hollywood for the film version of the latter, by Warner Brothers. A petite 4' 11" tall and with platinum blonde hair, Jewell appeared in a variety of supporting roles during the early 1930s. She played stereotypical gangster's women in such films as Manhattan Melodrama (1934) and Marked Woman (1937).

She was well received playing against type, as a seamstress sentenced to death on the guillotine, in A Tale of Two Cities (1935).

Her most significant role was as the prostitute Gloria Stone in Lost Horizon (1937).

In the mid-to late 1930s Ms. Jewell would, on occasion, go out to nightclubs with William Hopper (son of infamous gossip columnist Hedda Hopper and stage star DeWolf Hopper), but she never married.

Her subsequent films included Gone with the Wind (1939), Northwest Passage (1940), High Sierra (1941), and the low budget The Leopard Man (1943) but by the end of the 1940s her roles had reduced in significance to the degree that her performances were often uncredited.

By the end of her career she had appeared in more than one hundred films, between 1930 and 1971.

She died in Hollywood, California, aged 64, from undisclosed causes.

Isabel Jewell has a star on the Hollywood Walk of Fame for her contribution to motion pictures at 1560 Vine St.