Seneca was born Joel McGhee, Jr. in Cleveland, Ohio. Prior to his acting career, he belonged to the R&B singing group The Three Riffs, which was active from the late 1940s and performed at upscale supper clubs in New York City. He was also a Songwriter and had big hits with "Talk to Me" which was sung by Little Willie John, and "Break It to Me Gently," which was a smash hit twice, once by Brenda Lee in 1962 and once by Juice Newton in 1982.
Seneca appeared in Michael Jackson's "The Way You Make Me Feel" music video in the late 1980s.
In the 1982 film, The Verdict, Seneca plays the supporting role of Dr. Thompson, a small-town women's hospital physician brought in by attorney Frank Galvin (Paul Newman) to support his belief that two famous doctors' incompetence left his client alive but in a coma. Seneca's performance, while subdued, brings a gritty realism to the court proceedings and was one of his more important film roles. Arguably his most well-known roles are that of bluesman Willie Brown in Crossroads (1986) and Dr. Meddows in The Blob (1988), the evil head of a government team sent to contain the title creature.
Seneca played Eddie Haynes, on Matlock, in the May 9, 1989 episode "The Blues Singer." He later played a blind murder witness in the October 13, 1993 Law & Order episode "Profile."