Captain America and the Avengers is a one- to four-player (simultaneous) side-scrolling beat 'em up in which four Marvel Comics licensed heroes (Captain America, Iron Man, Hawkeye and Vision) take on the evil Red Skull, who, by assembling a team of super-villains, seeks to conquer the world.

The game consists of five stages, primarily focusing on side-scrolling brawler gameplay, but some of the levels also feature side-scrolling shooting stages, where the heroes battle menaces in the air (Stage 2), under the sea (Stage 3), and in space (Stage 5). Boss villains in the game consist of Living Laser and Klaw, Whirlwind, Grim Reaper, Wizard, Mandarin, Juggernaut, Ultron, Controller, Crossbones, and the Red Skull. In addition to the four playable Avengers, Quicksilver makes brief appearances to drop energy replenishments, and the Wasp can add protection and firepower in the shooting areas.