The first and the last are set in 1945, in an imaginary small German town ravaged by the war, Spitzen-on-the-Dein.

However, the story, told in a surrealistic, or anti-realistic, fashion, may be summarized by saying that the two parts of the novel set in 1945 depict the material and moral wasteland created by Nazism and World War II while the first part can be said to show the roots of those horrors in the years of earlier German imperialism and the humiliating defeat of 1918.

While the first and last part are told by a first-person narrator, Zizendorf, who masterminds a crackpot plot to kill Leevey, the American overseer of the occupied German town and start a rebellion of the defeated Germans against the Allied invaders, the central part is a third-person narrative where fragments of the past are told, describing episodes which involve Herman, the owner of a tavern and his son Ernst (who marries Stella), and a mysterious Englishman called Cromwell, who seems to have sided with the Germans against England but might also be a spy.

One of the earliest commentators of the novel, Albert J. Guerard, who taught Hawkes creative writing, maintains that "(...) the tiny, gutted Spitzen-on-the-Dein—with its feverish D.Ps., its diseased impotent adults and crippled children, with its foul choked canals, with its hunger, militarism, primitive memories and its unregenerate hatred of its conqueror—is Germany itself in microcosm".

Hawkes was praised by Thomas Pynchon, and it is likely that both The Cannibal and The Lime Twig were important sources of inspiration for his masterpiece Gravity's Rainbow.