Barrymore was born on April 28, 1878 in Philadelphia, Pennsylvania. He studied at the Episcopal Academy. Barrymore was married to Doris Rankin from 1904 until they divorced in 1923. Then he was married to Irene Fenwick from 1923 until they divorced in 1936. He had two daughters with Rankin, both died early. He had a fatherly love with Jean Harlow and treated her as if she was his own daughter. Barrymore died on November 15, 1954 in Van Nuys, California from a heart attack, aged 76.