The film follows the exploits of anthropologist Dr. Hess Green (Jones), who becomes a vampire after his intelligent but unstable assistant (Gunn) stabs him with an ancient cursed dagger.

One night, while staying in Green's lavish mansion, richly decorated with African art, his unstable assistant George Meda (Bill Gunn) threatens suicide.

The film ends with the young man Ganja had earlier killed rising out of the water, naked but alive, and running toward her, leaping over the corpse of Hess's servant Archie.

Gunn's artistic choices often defied conventional storytelling techniques, utilizing dreamlike sequences, elliptical editing, and experimental camera work to immerse the audience in the characters' experiences.

"[11] Writing in 2014, critic Scott Foundas described the film as a "landmark 1973 indie that used vampirism as an ingenious metaphor for black assimilation, white cultural imperialism and the hypocrisies of organized religion.

Piron interprets Gunn's approach in this way: "Moving back and forth between quiet interpersonal exchanges and vivid actions prompted by guilt and trauma over the deaths of the two title characters' spouses and their desire to reconnect to the Christian church, Ganja & Hess defies a traditional sense of linear structure.

Despite Heritage Enterprises' compromised release, the original cut was donated to the Museum of Modern Art, whose screenings, according to writer Chris Fujiwara, "helped build [the film's] reputation as a neglected classic of independent African American cinema.

"[15] Film critic and programmer Kelli Weston pointed out that while Gunn is "adept at subtlety, nuance, complexity, and allowing women the full depth of their own autonomy and independence," these are not among the creative traits of Spike Lee.

"[15] She went on to claim that the film's "status as a bona fide cult classic has been cemented over the past five years in particular," a development partly due to the fact that "over this period there have been these conversations about representation and the relationship with black people in front of the camera and also behind [it].