The 51-year-old director was in intensive care in a Los Angeles hospital since he had a stroke on April 17.
John Singleton, who made his movie directorial debut with the acclaimed "Boyz n the Hood" about young men struggling in a gang-ridden Los Angeles neighbourhood, died on Monday at the age of 51, his family said.
Singleton recently suffered a stroke, a family spokeswoman said.
"We are sad to relay that John Singleton has died," a statement from the family said.
"John passed away peacefully, surrounded by his family and friends."
Earlier on Monday, the family said it had made the "agonising decision" to withdraw life support from Singleton.
Singleton was a native of South Central Los Angeles, the community that was the setting for "Boyz n the Hood," a drama about friendship amid the peril of gang violence.
He became the first African-American and the youngest person to be nominated for an Academy award for best director, at age 24, for the movie.
Singleton later directed movies such as action film "2 Fast 2 Furious" and historical drama "Rosewood."
He is the creator and executive producer of current cable TV series "Snowfall" about the start of the cocaine epidemic in Los Angeles.
His family said Singleton "is a prolific, ground-breaking director who changed the game and opened doors in Hollywood, a world that was just a few miles away, yet worlds away, from the neighbourhood in which he grew up."