Early life
Lionel Barrymore was born Lionel Herbert Blythe in Philadelphia, the son of actors Georgiana Drew Barrymore and Maurice Barrymore. He was the elder brother of Ethel and John Barrymore, the uncle of John Drew Barrymore, Diana Barrymore, Sam, Ethel, and John Drew Colt and the grand-uncle of Drew Barrymore. Barrymore was raised a Roman Catholic. He attended the Episcopal Academy in Philadelphia, Pennsylvania.

In her autobiography, Eleanor Farjeon recalled that when she and Barrymore were friends as toddlers, she would take off her shoes and he would kiss her feet.

He was married twice, to actresses Doris Rankin and Irene Fenwick, a one-time lover of his brother John. Doris's sister Gladys was married to Lionel's uncle Sidney Drew, which made Gladys both his aunt and sister-in-law.

Doris Rankin bore Lionel two daughters, Ethel Barrymore II (b. 1908) and Mary Barrymore (b. 1916). Neither child survived infancy, though Mary lived a few months. Barrymore never truly recovered from the deaths of his girls, and their loss undoubtedly strained his marriage to Doris Rankin, which ended in 1923. Years later, Barrymore developed a fatherly affection for Jean Harlow, who was born about the same time as his two daughters and would have been about their age. When Jean died in 1937, Lionel and Clark Gable mourned her as though she had been family.

Stage Career
Barrymore began his stage career in the mid-1890s, acting with his grandmother Louisa Lane Drew. He appeared on Broadway in his early twenties with his uncle John Drew Jr. in such plays as The Second in Command (1901) and The Mummy and the Hummingbird (1902), both produced by Charles Frohman. In 1905 Lionel and his siblings, John and Ethel, were all being groomed under the tutelage of Frohman. That year Lionel appeared with John in a short play called Pantaloon while John appeared with Ethel in Alice-Sit-By-The-Fire.

In 1910, after he and Doris had spent many years in Paris, Lionel came back to Broadway, where he established his reputation as a dramatic and character actor. He and his wife often acted together on stage. He proved his talent in many plays, including Peter Ibbetson (1917) (with brother John), The Copperhead (1918) (with Doris), and The Jest (1919) (again with John). Lionel gave a short-lived performance as MacBeth in 1921. The play was not successful and more than likely convinced Lionel to permanently return to films. One of Lionel's last plays was Laugh, Clown, Laugh (1923) with his second wife, Irene Fenwick. This play would later be made into a 1928 silent film starring Lionel's friend, Lon Chaney, Sr.