DeSoto was born in San Jose, California on September 2, 1950. Both of her parents were Mexican immigrants from Michoacán. DeSoto had four brothers and four sisters, making her one of nine siblings. She spent her early years handpicking fruit, particularly apples.

From 1974 to 1978, DeSoto was married to Jonathan Taplin. They have one daughter, Daniela (born June 1976).

DeSoto made her film debut in 1979 with The In-Laws. She appeared opposite Nick Nolte and Debra Winger in Cannery Row (1982). DeSoto won the Golden Eagle Award for Best Actress for her performance in The Ballad of Gregorio Cortez (1982). In 1986, she appeared opposite Rob Lowe and Demi Moore in About Last Night, playing Mrs. Lyons. That same year, she portrayed waitress Diana Olmos in the short-lived sitcom, The Redd Foxx Show.

In 1987, DeSoto appeared in the biographic film La Bamba. In that film, she portrayed Connie Valenzuela, the mother of Ritchie Valens, played by Lou Diamond Phillips. The next year, DeSoto collaborated with Phillips again in the 1988 biopic Stand and Deliver, where she portrayed Fabiola Escalante, the wife of Jaime Escalante (Edward James Olmos). Her performance garnered her an Independent Spirit Award for Best Supporting Female.

In 1989, she played the wife of Dustin Hoffman’s character in Family Business. That same year, she landed the principal role in Face of the Enemy. She also played Azetbur in Star Trek VI: The Undiscovered Country (1991). DeSoto portrayed Linda in The 24 Hour Woman (1999). She has also acted in the soap opera, The Bold and the Beautiful.

DeSoto wrote and appeared in “A Woman in Progress/Canto de Oro, Cuento de Mujer” that was produced by the Intar Theater group in New York in 2005.