In 1920's New York City, jazz is on the rise. PaPa LaBas lives in Harlem where he works as a voodoo practitioner. Along with Black Herman, PaPa resists the Wallflower Order, an attempt to rid New York of culture by way of dogmatic monotheism (some worship the Egyptian sun-god, Ra). The Wallflower Order views jazz culture as a viral infection of society, and they seek to eliminate the "carriers" of that disease. They call the movement, "Jes Grew," and the carriers, they call "Jes Grew Carriers," or JGC for short.
PaPa begins his resistance by trying to find a mysterious book that was taken by a black militant (like a zealot) named Hamid. The black militants are often Islamic in inclination, which Hamid is partially responsible for (he was born Eugene Brown). The racial conflict between black people and white people is demonstrated as a worldwide issue, resulting in the mistreatment of African nations. In a sub-plot, the Wallflower Order Atonists (who worship Ra) try to find a black man who will say and do what they want.
The novel coincides with the Harlem Renaissance, and the novelist includes Malcolm X, W.E.B Du Bois, and many of the authors from the Harlem Renaissance movement. PaPa offers a paraphrase of the Bible's stories, but apparently, in the Mumbo Jumbo universe, the Bible contains different stories than the real Bible does, including stories about Seth and Osiris (Egyptian gods), Dionysus (a Greek god) and Faust (from Goethe).
In 1970, PaPa looks back on the Jazz Age and realizes that the 1970's have the same sense, but this time instead of black people bringing Jazz into the culture, they're bringing the Funk.
The novel is written chaotically without typical novel structures, but the beginning and end are written like segments of a screenplay.