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Immigrated to the U.S.A. in 1912.

He is the only actor to have appeared in both the 1931 Paramount film version of Il dottor Jekyll (1931) and in the film Il figlio del Dott. Jekyll (1951), although he received no screen credit in the latter film.

Some sources give his birth name as Edward Sanger.

From 1928, in roughly 135 films, including shorts and silent, until his first Sherlock Holmes movie in 1939, Holmes Herbert acted under H.E. Herbert, H.J. Herbert, and Holmes E. Herbert. It does not appear that he took the name "Holmes" in deference to the six Sherlock Holmes' films in which he appeared.

Appeared in eight Academy Award for Best Picture nominees: La casa dei Rothschild (1934), Capitan Blood (1935), Emilio Zola (1937), La leggenda di Robin Hood (1938), Maria Antonietta (1938), Il prigioniero di Amsterdam (1940), Ombre malesi (1940) and Johnny Belinda (1948). Only The Life of Emile Zola won.

He appeared in three films that have been selected for the National Film Registry by the Library of Congress as being "culturally, historically or aesthetically" significant: L'uomo invisibile (1933), Emilio Zola (1937) and La leggenda di Robin Hood (1938).

It is often believed he chose his stage name out of respect for one of his favorite literary characters, Sherlock Holmes. However, it is more likely that the name was a combination of his father's stage name, Ned Herbert, and the surname of one of his later music hall contemporaries and comedy partner.