The Amazing Adventures of Kavalier and Clay recounts the turbulent coming of age of Joe Kavalier and Sam Clay.  The novel begins in 1939: Josef Kavalier has just arrived in Brooklyn, having escaped Nazi-occupied Prague.  In the darkness of his aunt’s tiny flat he meets his cousin, Sammy Klayman.  Joe is teetering on the brink of despair.  His sole aim is to earn enough money to get his family to America, as quickly as possible.  Sammy’s woes are of a more conventional sort – his dreams of turning himself into a great man are frustrated by self-doubt and limited opportunity.  Within hours of the cousins meeting, however, Sammy has hatched a money-spinning plan, and the partnership of Kavalier and Clay is born.  Inspired by Sammy’s wild imagination, with Joe’s impressive art work, a brand new comic book superhero is born.  Kavalier and Clay’s all-American star, the Escapist, is an immediate sensation.

Through the Escapist, Joe wages his private war against Hitler and the Nazis, using increasingly violent and unsubtle imagery as his fear for his family, and frustration with America's neutrality, increases.  Joe takes to seeking out New York City’s German enclaves, picking fights and getting soundly beaten up, the only way he has of tackling his impotency and rage.  On one such foray he encounters Carl Ebling, the apparently lone representative of the Aryan-American League.  While Joe sees Carl as one more German with whom to pick a fight, Carl takes things rather further; he makes it his quest to destroy Joe and the Escapist, employing the techniques of a comic-book super-villain (fortunately not very successfully).

Quite by chance, Carl’s sister Ruth turns out to be the ruin of Sammy’s happiness.  While the Escapist has brought him fame and some measure of fortune, Sam is struggling to come to terms with the realisation that he is gay.  The object of his affection is the Escapist himself, or at least the handsome young actor who voices him on radio.  Sam’s chance at happiness is brought crashing down during a brutal police raid, and he chooses denial and conventionality rather than following his heart. 

Joe, meanwhile, on the brink of starting a new life with his beloved Rosa, has happiness snatched from him by a German U-Boat.  Mad with grief, remorse and anger, he enlists in the American navy. But instead of being sent to fight in Europe or Asia, he finds himself posted to the inhospitable Antarctic, with only a radio for company.

In his loneliness and isolation, Joe persuades himself that Rosa and Sam are getting on with their lives and are better off without him.  Following the end of the war, instead of returning to those he loves, he disappears for several years.  Sam and Rosa continue to hope that they’ll be reunited with him eventually.  A bizarre sequence of events finally brings everyone together again, and the partnership of Kavalier and Clay is restored, but with a new twist.