Collins was born in Sacramento, California to Lillie Bidwell and William C. Collins, a newspaper drama editor. He started acting on stage at the age of 14. In the mid 1930s, now an established stage and radio actor, Collins began working with Orson Welles' Mercury Theatre leading to some of his most memorable roles. Having already appeared on radio with Welles on The Shadow (a regular as Commissioner Weston) and in Welles' serial adaptation of Les Miserables from 1937, Collins became a regular on The Mercury Theatre on the Air; through the run of the series, he played many roles in literary adaptations, from Squire Livesey from Treasure Island and Dr. Watson to Mr. Pickwick in an adaptation of Pickwick Papers. Collins' best known (albeit uncredited) work on this series, however, was in the infamous The War of the Worlds broadcast, playing three roles, including Mr. Wilmuth (on whose farm the Martian craft lands) and the newscaster who describes the destruction of New York.
Along with other Mercury Theatre players, Collins made his first notable screen appearance in Citizen Kane, as ruthless Boss Jim Gettys. He would also play key roles in Welles' The Magnificent Ambersons and Touch of Evil. Collins appeared in over 90 films in all, including Leave Her to Heaven (1945), The Best Years of Our Lives and Crack-Up (1946), A Double Life (1947), two entries in the Ma and Pa Kettle series (as in-law Benjamin Parker), and the 1953 version of The Desert Song, in which he played the non-singing role of Kathryn Grayson's father. He displayed comic ability in The Bachelor and the Bobby-Soxer (1947), and The Man from Colorado (1948).
He may be best remembered for his work on television, playing Lieutenant Tragg on Perry Mason in the 1950s and 1960s. He was also a regular as John Merriweather on the television version of The Halls of Ivy starring Ronald Colman.