The son of the English comedian Edward Askew Sothern, he made his first stage appearance with his father's company in New York City in 1879. He toured England in 1882 and 1883 and became leading comedian in John McCullough's company. Under Daniel Frohman he was leading man at the Lyceum Theatre in New York and in 1899 formed his own company. In 1900 Sothern appeared in the title role of Hamlet, in 1901 in that of Richard Lovelace, and in 1902–03 as Villon in If I Were King, three of his greatest roles. In 1904 he played opposite Julia Marlowe (Marlowe, Julia) in Romeo and Juliet in Chicago. Thereafter, except for 1907–09, they appeared together on the stage almost continuously until their retirement in 1924. They were married in 1911. Sothern had a repertory of over 125 parts, but he was best known as the romantic hero in plays such as The Prisoner of Zenda. His autobiography, The Melancholy Tale of Me, was published in 1916.