Ontiveros' son Elias said the actress died Thursday night at Presbyterian Hospital in Whittier with her family by her side.
Ontiveros had a 35-year career in Hollywood, but she was best known for playing Yolanda Saldivar, the woman who murdered singer Selena, in the 1997 film "Selena," starring Jennifer Lopez.
She also appeared on ABC's "Desperate Housewives" as Juanita Solis, the mother-in-law of Eva Longoria's character Gabrielle, which earned her an Emmy nomination in 2004.
Longoria tweeted about Ontiveros' death, saying, "I'm deeply saddened at the news of my dear friend Lupe Ontiveros passing. She was more than a colleague to me, she was my family. My heart is with your family Lupe."
Ontiveros also appeared in dozens and TV shows, including "As Good As It Gets," "The Goonies," "Weeds" and "Southland."
L.A. Mayor Antonio Villaraigosa released a statement on her death, calling her "one of the most prolific Mexican American actresses of our time."
"It is with deep sadness yet much pride that we reflect upon a woman whose immense contributions opened the door for Latinos and touched so many through her artistic talent," he said. "My thoughts and prayers are with her family and friends during this difficult time."