Firmin is born the youngest rat in a large litter to a rat named Flo. Desperate for a place to deliver her litter, Flo enters a bookstore belonging to Norman Shine. In an attempt to provide a nest, she shreds (as we later learn) Finnegans Wake by James Joyce. As the runt of the litter, Firmin is unable to feed regularly, leading to his habit of eating books. It starts with the nest, but soon moves on to new books.

Eventually, Firmin realizes he can read, and thus his obsession with literature begins. Not long after, his mother leaves the bookstore, and the rest of the family follows soon after. Firmin, however, remains behind and spend his days watching Norman tend to the store from a gap in the ceiling Firmin calls the Balcony, and his nights reading or scrounging for food. One of his favorite spots to find food is the Rialto, a movie theater that after midnight shows pornography. Firmin falls in love with woman, referring to them as his Lovelies.

One morning, Norman spies Firmin from watching from his perch in the ceiling, and so he places rat poison in the ceiling. Firmin eats some of it, starts to become sick, and then learns that he has been poisoned. Angry and betrayed (for Firmin had fallen in love with Norman, developing a rich tapestry of imaginary events occurring between them) Firmin loses some of the attachment he had to the bookstore and to Norman. One day he heads to the park with the intention of using some sign language he had learned to communicate with a human. Unfortunately, his attempt fails and he is attacked, but he survives with damage to a leg. Desperate for food, he leaves his shelter in the park to get food being fed to squirrels. Jerry Magoo, a local author who frequented the bookstore, sees him and rescues him.

For the next 6 months Firmin spends his time with Jerry, playing a piano and listening to Jerry talk. Though Jerry catches Firmin reading, Firmin is convinced that Jerry does not actually think Firmin can read, and always envisions him as a cute animal, and nothing more sophisticated. One night returning to his apartment, Jerry has a stroke and he falls down the stairs. Firmin is stuck in the apartment and must wait to hear what has happened until the next day from his spot in the Balcony. Within a few days, Jerry"s family comes back to the apartment and they clear out his things, leaving us to assume he has died.

Not long after, the bookstore is destroyed in a demolition effort to rebuild the area. Firmin, who just had a vision of Ginger Rogers giving him a striptease, finds a quote from Finnegans Wake as his life ends under the crush of rubble.