Diary of a Wimpy Kid details protagonist Greg Heffley's first year of middle school, a key transition point in adolescent life. The story is told through Greg's eyes and reveals his sensibilities and perceptions as the school year unfolds.

Greg is presented in the graphic novel as a typical middle school kid from a typical family, which seems to be squarely middle class. Greg is a self-labeled wimp, because he shuns sports and physical exercise in favor of video games. He has an older brother, Rodrick, and a younger brother, Manny (a toddler). His best friend is Rowley Jefferson, a sweet boy whose naïveté consistently embarrasses Greg. On the first day of middle school, for instance, Rowley asks Greg if he wants to "play" after school—despite Greg's repeated reminders to use the phrase "hang out" instead of "play" now that they are in middle school.

The book illustrates a series of incidents Greg and his friends encounter throughout the course of the school year. They are presented in the form of selected entries from Greg's diary, detailing his thoughts and emotions as he deals with each incident and progresses through school. The book is formatted so that the words look as though they are written on lined notebook paper.

Diary of a Wimpy Kid relates themes and situations that, while unique to Greg in the story, are also representative of American middle school life. Like most middle-schoolers, Greg is obsessed with being popular, so he tries out for the wrestling team, and later for the school play. He tries to avoid classmates such as Fregley, the school nerd, and is frustrated with Rowley's immaturity. Throughout the year, Greg makes some unethical decisions—hiding competitors' drawings to earn a cartoonist position, letting Rowley take the blame for something that was his fault—pulls a typical middle school Halloween prank, and deals with school bullies.

At the end of the story, though, Greg stands up for Rowley after older students bully Rowley into eating a piece of moldy cheese that has been on the playground all year. This incident illustrates the inner growth that Greg, along with his friends, has achieved. As he and Rowley make plans for summer, it is apparent that Greg is more comfortable with middle school now and more comfortable with his own identity—issues that are explored further in a series of Diary of a Wimpy Kid sequels.