The summer before Remus began his tenure as the Defence professor, Sirius Black escaped from Azkaban. Remus, like the rest of the wizarding world, believed that Sirius had betrayed the Potters to Voldemort and murdered Peter Pettigrew.

By the end of the school year, however, Remus knew the truth of what had happened and that Pettigrew was still alive, hiding in his Animagus form — Scabbers, the pet rat of Ron Weasley. He was watching the Marauder's Map, expecting Harry and his friends to go down to see Hagrid before Buckbeak's execution and was shocked to see Pettigrew coming out of Hagrid's with them. Remus was reunited with his old friend Sirius, and the two resolved to kill Pettigrew for his part in the deaths of James and Lily and in framing Sirius. They were stopped by Harry Potter, who believed it would be better to hand Pettigrew over to the Ministry of Magic to prove Sirius' innocence, and also did not think his father would want Remus and Sirius to become killers.

However, that night happened to be a full moon, and Remus transformed into a werewolf (having forgotten to take the Wolfsbane Potion). Sirius was forced to turn into his Animagus form to protect Harry, Ron and Hermione from Remus. In the chaos, Pettigrew unfortunately escaped and would later return to his master. Once in the forest, Lupin proceeded to attack Harry and Hermione, but was stopped by Buckbeak the hippogriff. After the attempted attack on Harry and Hermione, Remus spent the rest of the night deep in the Forbidden Forest.