The Thundergun is a large, cannon-shaped weapon that fires blasts of incredibly strong compressed air. It has no iron sights, meaning it must be fired from the hip (although when observed in third person, it is held on the shoulder). It is able to kill large numbers of zombies with a single shot, sending them flying backwards or up. Those who are not killed by the blast are thrown backwards and will remain on the ground for a few seconds before getting back up. The Thundergun holds two rounds in its magazine, and has 12 rounds in reserve. The Thundergun can only be reloaded when all shots have been fired. The Thundergun is important during the later rounds as it is useful for clearing large groups of zombies in order to reach a downed teammate or make an escape. It is extremely useful when swarmed as it will easily kill a large group of zombies in one shot.

It is often used as a reserve weapon, as it has a low amount of ammunition and a moderately slow reload. It can only be reloaded when the entire magazine is empty, except in the campaign mission "Numbers", where one is able to execute a partial reload, and on the Wii version of the game. Because of this, it is advised to shoot any extra rounds in a magazine before obtaining a Max Ammo power-up. Wasting ammo on one zombie or a small group is not advisable. It is also a decent weapon against Hellhounds as it can easily take large numbers of them out and will always kill them in one hit, with there also being a Max Ammo power-up at the end of a Hellhound round.