Otis was a neighbour of Hershel Greene and a regular farm hand before the undead apocalypse. He and his wife Patricia took up permanent residence on the Greene Farm during the outbreak, remaining relatively isolated while urban areas became mass graves as the zombie plague spread. Otis was an experienced hunter and would often go out to hunt game for the family. He encountered Rick Grimes and his group of Atlanta survivors while hunting a deer in the woods, during which he accidentally shot Rick's son Carl.
Otis led Rick to the Greene Farm to get help for Carl, but Hershel did not have all the necessary tools with which to save the boy. Taking responsibility for Carl's injury, Otis offered to go into the nearby town to find a respirator and Shane went with him.
In the episode "Save The Last One", Shane and Otis find the supplies they need to help Carl inside a high school. However, walkers are swarming all over the place and Shane sprains his ankle while trying to jump out of a window. Injured, low on ammo and pursued by zombies, Shane fears that he and Otis will both be eaten and Carl will die as a result. To ensure that Carl gets the treatment he needs, Shane uses his last round to cripple Otis by shooting him in the leg. Shane then takes Otis' pack and gear, though the outraged Otis struggles and fights Shane. Shane pistol-whips Otis into letting go of him and he runs while Otis is swarmed by the undead and eaten alive.