The Gish sisters' mother Mary began acting in order to support the family after her husband abandoned them. When Lillian and Dorothy were old enough, they joined her act. They also took modeling jobs. In 1914, they met Mary Pickford, and she got them contracts with Biograph studios. Their first role was in An Unseen Enemy, directed by D.W. Griffith. The Gish-Griffith association was so close that it has been widely suspected that Lillian was Griffith's lover, though the evidence is circumstantial at best. Known relationships were Lillian's affairs with Charles Duell, a producer, to whom she was reportedly engaged, and the drama critic and editor George Jean Nathan.
Having appeared in over 25 short films and features in her first two years in Hollywood, Lillian became a major star, becoming known as "The First Lady of the Silent Screen". Preferring silent movies, she spurned talkies until MGM finally let her go from her contract in 1928. She acted on the stage for the most part in the 1930s and early 1940s, prefering to care for the aging Griffith and his wife in their later years.
Returning to movies, Gish was nominated for the Academy Award for Best Supporting Actress in 1946 for Duel in the Sun. She appeared in films from time to time for the rest of her life, in 1971 winning a special Academy Award "For superlative artistry and for distinguished contribution to the progress of motion pictures." In 1984 she received an American Film Institute Lifetime Achievement Award.