After playing in Boston and touring in the U.S., he sailed for England, making his London debut in 1881 on a double bill as Mr. Sharpe in False Colours and Marshley Bittern in Out of the Hunt.
Back in New York, in 1884, he played Eliphaz Tresham in The Fatal Letter, Melchizidec Flighty in Whose Are They?, which he wrote himself, and in Nita's First.
The next year, he was Alfred Vane in Favette, Knolly in Mona, John in In Chancery and Jules in A Moral Climate.
He was hired by Charles and Daniel Frohman in the stock company of the old Lyceum Theatre in New York, where he starred as a leading man for the next twelve years.
He was especially known for his heroic portrayal of Rudolph Rassendyl in the first stage adaptation of The Prisoner of Zenda, by Anthony Hope, which he first played in 1895.
He finally opened the play in New York in 1900, but during the first week, he was stabbed in the foot by Laertes' sword and was stricken with blood poisoning, closing the production.
[2] In 1904, he began an extremely successful partnership with actress Julia Marlowe, beginning with their appearances as the title roles in Romeo and Juliet, Beatrice and Benedick in Much Ado About Nothing, and the leads in Hamlet.
Sothern played Raskolnikov in Laurence Irving's adaptation of Crime and Punishment, entitled The Fool Hath Said in His Heart.
He also starred in Hamlet and If I were King, as well as playing Lord Dundreary, his father's famous role, in Our American Cousin.
[2] At the end of 1909, Sothern and Marlowe reunited in Antony and Cleopatra at the New Theatre in New York under the direction of Louis Calvert.