The story explores themes of discontent and alienation, especially within families. Elements of the novel seem autobiographical, particularly in passages about Jimmy's estranged relationship with his father (Ware only met his father once in adulthood, during the period he was working on this book, and has remarked that his father's attempts at humor and casualness were not unlike those he'd already created for Jimmy's father in the book). However, it should not be read as a direct account of Ware's personal life. There are also many flashback scenes, including a substantial narrative set in the Chicago World's Columbian Exposition of 1893. The 1893 sections follow Jimmy's grandfather as a lonely little boy and his difficult relationship with an abusive father (Jimmy's great grandfather). As several elements from the past and the present eventually intersect, albeit subtly, it can be said that the book is also a Corrigan family chronicle.
Ware's novel, like his other work, is heavy with symbolism and visual storytelling, exploring and demonstrating the potential of the comics medium. Many pages are devoid of text, and some contain complex iconic diagrams. Notable leitmotifs in Jimmy Corrigan include the robot, the bird, the peach, the miniature horse, and the flawed Super-man figure (seen also as a father figure and as God).
In addition to the graphic novel, the character of Jimmy Corrigan has appeared in other Ware comic strips, sometimes as his imaginary child genius character, sometimes as an adult. Corrigan, in fact, began as a child genius character in Ware's early work, but as Ware continued, the child genius strips appeared less frequently as we increasingly followed Corrigan's sad, adult existence.
Occasional, more realistic flashback strips showing Jimmy as a lonesome child of divorce suggest that this was Jimmy's "real" childhood, while his "Smartest Kid on Earth" adventures are his fantasies... although, Jimmy being Jimmy, even his fantasies tend to end in disaster.
The earlier "Acme Comic Library" strips complicate the totality of the award-winning graphic novel. Some contend that The Acme Novelty Library serialized Jimmy Corrigan alongside strips featuring other dark, surreal Ware characters like "Big Tex", "Rocket Sam" and "Quimby the Mouse," and these characters could also be taken as extensions of Jimmy's fantasy life. Others suggest that this is an angular take on the character of Jimmy, when Ware was more interested in revising nostalgic or retro themes with his dark humor.