Born in Aledo, Illinois, Henderson was a classically trained musician who later attended Harvard College.

He entered film with the Thanhouser Company in late 1910, functioning as chiefly a director.

[citation needed] He was working for Universal Studios by 1915 and later claimed to have been the first to recognize the potential of Rudolph Valentino.

However, in 1923 he resurrected his interest in movies and rekindled his abilities as an actor, starring in a number of films in the mid-1920s.

The oldest living member of the Lamb's Club, Henderson was honored with a testimonial dinner in 1942.