Leon is one of the two protagonists in Resident Evil 2; the other being Claire Redfield. In the story, Leon is a recently-hired police officer for the Raccoon Police Department. He arrives late to Raccoon City on his first day. He finds the town already overrun by zombies and encounters a civilian, Claire. The two decide to seek refuge in the city's police station, and they attempt to escape the city alive. He maintains radio contact with Claire and is partnered with Ada Wong, a woman claiming to be looking for her missing boyfriend. His attempt to find an escape route leads him to Umbrella's underground laboratory within the city, where he confronts several of Umbrella's mutant creatures, including Umbrella's prize creation, the Tyrant. Just prior to making his escape, Leon learns that Ada is actually working for a rival corporation of Umbrella's and was sent to steal the G-Virus. Ada is mortally wounded during an encounter with the Tyrant and is presumed to die from it, however, leaving Leon to escape along with Claire and Sherry Birkin.
The epilogues of Resident Evil 3: Nemesis expand on Leon's fate following Resident Evil 2. After escaping the city, Claire set out on her own to search for her brother, while Leon and Sherry were approached by the US military, and Leon made an undisclosed deal with a representative of the US government. In Resident Evil: Survivor and Resident Evil Code: Veronica Leon has joined an anti-Umbrella force. In Survivor, he is mentioned to be the one who sent the game's protagonist, Ark Thompson, to Sheena Island. In Code: Veronica, Claire gets in touch with Leon when she is trapped on Rockfort Island, and Leon relays the information to Chris Redfield.
Leon returned as the protagonist of Resident Evil 4. Set six years after the events of Resident Evil 2, Leon has become an agent for the US government and is assigned to rescue the newly-elected President's daughter, Ashley Graham, who is being held at an undisclosed location. Her kidnappers turn out to be part of a cult known as Los Illuminados, which has taken control of the local villagers with parasites known as Las Plagas. Leon teams up once again with Ada Wong, who seeks to steal the Plagas sample for her unknown employer, and Luis Sera, a former researcher for Osmund Saddler, the cult leader. He also confronts Jack Krauser, a former acquaintance who disappeared two years prior to the events of the game, now working for Albert Wesker.