He died Monday in Los Angeles at age 72, Drew Barrymore said in a statement issued by her publicist. No information was released about the cause of death.
"He was a cool cat. Please smile when you think of him," Barrymore said in the statement.
He was part of an acting clan that included his father, the famed stage and film actor John Barrymore, his mother, silent screen star Dolores Costello, and his father's siblings, Lionel and Ethel Barrymore. Drew Barrymore is his daughter by his third wife, Ildiko Jaid Barrymore.
He started his career as a teenager, billed first as John Barrymore Jr., with early roles in the 1950s movies "The Sundowners," "High Lonesome," "Quebec," "The Big Night," "Thunderbirds" and "While the City Sleeps."
But there were problems with drugs, drunken driving and violence, domestic and otherwise. By the early 1960s he had left Hollywood for Italy, working in European movies.
In a 1962 interview with The Associated Press in Rome he made no apologies for headline-grabbing street brawls there.
"I'm not a nice, clean-cut American kid at all," he said. "I'm just a human being. Those things just happen."
By 1964 he had been married twice, to Cara Williams and to Italian actress Gabriella Palazollo, and had returned to Hollywood after making more than a dozen films overseas -- none of them any good by his own estimation.
By then his billing had become John Drew Barrymore, perhaps to step out of his father's shadow.
"I don't mind if my acting is compared to him," he said in an AP interview. "The trouble is that people expect me to live like him."
In 1967, he was convicted of possession of drug paraphernalia -- cigarette papers -- but acquitted of being in a place where marijuana was being smoked. The judge rejected the prosecution's urging to throw Barrymore into jail, and instead put him on probation.
"Take advantage of your talent and I think you'll go far," Municipal Judge Theodore G. Krumm told him.
Barrymore later had sporadic film and television roles.
As a teenage star battling alcoholism herself, Drew Barrymore wrote about her father in the memoir "Little Girl Lost." He was depicted as menacing, showing up only to abuse his daughter and former wife and ask for money.
John Drew Barrymore was born in Beverly Hills on June 4, 1932. Besides his other famous relatives, his grandfather was the early film idol Maurice Costello, his aunt on his mother's side was 1920s star Helene Costello, and his older half sister was the actress Diana Barrymore, who described her troubled life in her memoir, "Too Much, Too Soon," and died in 1960 at age 38.
Barrymore is also survived by a son, John Barrymore III, by his first wife.