Set in Harlem, Amos 'n' Andy centered around the activities of George Stevens, a conniving character who was always looking for a way to make a fast buck. As head of the Mystic Knights of the Sea Lodge, where he held the position of "Kingfish," he got most of the lodge brothers involved in his schemes. That put him at odds not only with them, but with his wife, Sapphire, and her mother. Mama, in particular, didn't trust him at all. Andy Brown was the most gullible of the lodge members, a husky, well-meaning, but rather simple soul. The Kingfish was constantly trying to swindle him in one way or another, but the "big dummy" (as Kingfish called him) kept coming back for more. More often than not, Kingfish would get them both into trouble, but win Andy's cooperation with an appeal to fraternal spirit--"Holy mackerel, Andy! We's all got to stick together in dis heah thing...remember, we is brothers in that great fraternity, the Mystic Knights of the Sea."

Amos was actually a rather minor character, the philosophical cabdriver who narrated most of the episodes. Madame Queen was Andy's friend and Lightnin' was the slow-moving janitor at the lodge.

Civil rights groups such as the NAACP had long protested the series as fostering racial stereotypes, to little avail. Amos 'n' Andy drew sizable audiences during its two-year CBS run, and was widely rerun on local stations for the next decade. The turning point came in 1963 when CBS Films, which was still calling Amos 'n' Andy one of its most widely circulated shows, announced that the program had been sold to two African countries, Kenya and Western Nigeria. Soon afterward, an official of the Kenya government announced that the program would be banned in his country. This focused attention a new on the old controversy and in the summer of 1964, when a Chicago station announced that it was resuming reruns, there were widespread and bitter protests. CBS found its market for the films suddenly disappearing, and in 1966, the program was withdrawn from sale, as quietly as possible.

As to whether the program was in fact racist, there was no agreement on that. The creators certainly didn't think so, and actor Alvin Childress (Amos) was quoted as saying, "I didn't feel it harmed the Negro at all....Actually the series had many episodes that showed the Negro with professions and businesses like attorneys, store owners, and so on, which they never had in TV or movies before..." Others pointed out that the situations were no different than those found in many comedy programs with white characters. Nevertheless the humor certainly derived from the fact that these were shiftless, conniving, not-too-bright blacks. The very stereotypes that had so long been unfairly applied to an entire race were used throughout. As a result, it is unlikely that Amos 'n' Andy will ever be seen again on television.