Born in Fort Dodge, Iowa to a Russian Jewish family, Arkoff first studied to be a lawyer. Along with business partner James H. Nicholson and producer-director Roger Corman, he produced eighteen films. In the 1950s, Nicholson founded the American Releasing Corporation, which later became known as American International Pictures, and made Arkoff the vice-president. AIP films were mostly low-budget, with production completed in a few days, though nearly all of them became profitable.

Arkoff is also credited with starting a few genres, such as the Beach Party and outlaw biker movies, and his company played a substantial part in bringing the horror film genre to a novel level with successes such as Blacula, I Was a Teenage Werewolf and The Thing with Two Heads. American International Pictures movies starred many established actors in principal or cameo roles, such as Boris Karloff, Elsa Lanchester and Vincent Price, as well as others who later became household names, including Don Johnson, Nick Nolte, Diane Ladd, and most notably Jack Nicholson. A number of actors shunned or overlooked by most of Hollywood during the 1960s and 1970s, such as Bruce Dern and Dennis Hopper, also found work in one or more of Arkoff’s productions. Arkoff’s most financially successful film was the 1979 adaptation of Jay Anson’s book The Amityville Horror.

Not long after American International Pictures went out of business, Arkoff founded Arkoff International Pictures.

Arkoff began his career in Hollywood as a producer of The Hank McCune Show, a seminal sitcom produced in 1951. He innovated the TV laugh track rather than go to the expense of a studio audience.
In 2000, Arkoff was featured alongside former collaborators including Roger Corman, Dick Miller and Peter Bogdanovich in the documentary SCHLOCK! The Secret History of American Movies, a film about the rise and fall of American exploitation cinema.

Arkoff died in 2001, within weeks of his wife’s death.