Red Dead Redemption is a free-roaming western game and the spiritual successor to Red Dead Revolver. The game is set in 1911, where players take control of John Marston, an outlaw who is forced to turn on his peers when federal agents threaten his family. He is sent to the American frontier to capture his former gang members, especially the notorious leader Bill Williamson.

In the open world, the player is free to follow the storyline or partake in the various events that occur while exploring the West; similar in overall design to Rockstar's Grand Theft Auto series. Horses are the main means of transportation, and the player can whistle for their mount at any time. Players can also visit towns, talk to other characters, and join or intervene in events such as public hangings, ambushes, and robberies. Many of these are random, including dangerous animal attacks and bandit ambushes. Other activities include hunting, gambling, duels, and standoffs, with guns as the main weapon.

Based on the player's decisions, two morality systems (honor and fame) influence how the environment and other characters react to Marston. Marston can shoot while riding a horse and capture people by lasso, combined with a cover system with specific targeting or wildfire. In the recharging "Dead Eye" targeting mode, time is slowed down to target different enemies in specific locations, and then execute the shots in rapid succession. The player can also set up camps anywhere in the world to fast travel to known locations or save their game.

Multiplayer is supported through free-for-all, team, and capture-the-flag modes, introducing crates with weapons and power-ups. Games start with a Mexican standoff where the survivor receives some extra time to gather items while the others are respawning. Similar to Grand Theft Auto IV, there is a continuous free-roaming mode where players can team up in posses to form a party and engage computer-controlled gangs. Posses are made up of a maximum of eight players and all multiplayer games support a maximum of sixteen players. During multiplayer, the characters can level up and gain access to new mount breeds, character models, and weapon skins.