The film tells the story of four generations of an immigrant family of musicians whose careers parallel the history of American popular music in the 20th century.

When Zalmie's mother dies in the Triangle Shirtwaist Factory fire, he begins working with Louie full-time at a small theatre.

When World War I strikes, Zalmie travels the globe performing for the troops as the bottom half of a pantomime horse and sustains a wound to his throat during a German air raid, which ends his singing career.

When Zalmie returns to New York, he briefly continues performing as a clown, and falls in love with a stripper named Bella, vowing to make her a famous singer and getting involved with mobsters in order to do so.

Benny marries Palumbo's daughter at Zalmie's request and enlists to fight in World War II seeking redemption for his family, despite pleas from his father.

Benny's wife and son, named Tony, now live in a suburban Long Island town, and they watch as Zalmie testifies against Palumbo on television, calling him a rat.

The band becomes successful but slowly starts to decompose because of the heroin addictions of female lead singer Frankie Heart and Tony himself.

As the result of his reputation as an innovator of adult animation, Bakshi was able to acquire the rights to an extensive soundtrack, including songs by Bob Dylan, Jefferson Airplane, Janis Joplin, The Doors, George Gershwin, The Mamas & the Papas, Herbie Hancock, Lou Reed and Louis Prima, for under $1,000,000 in permissions fees.

"[13] Michael Barrier, an animation historian, described American Pop as one of two films that demonstrated "that Bakshi was utterly lacking in the artistic self-discipline that might have permitted him to outgrow his limitations.

[3][15] Ain't It Cool News head writer Harry Knowles wrote that American Pop was his favorite Ralph Bakshi film.

[18] At the Aero Theatre in Santa Monica, California on March 27, 2015, there was a screening of American Pop with director Ralph Bakshi, Ron Thompson and Mews Small attending.