In the game, players take place in the role of Rango the chameleon and the game takes place in the Mojave Desert. The game currencies are sheriff stars that can be obtained by killing enemies, smashing objects, etc. More sheriff stars are earned when they melee enemies, uppercut and shoot the enemies in the air. A gun was used as Rango's weapon which they can use it to shoot enemies and levers. When they go to a golden bullet, the bullet must hit all the targets. A bullseye earns more sheriff stars when hit. They ride on various objects, including roadrunners, spaceships, bats and Mr. Timms. In order for players to get a 100%, they must mine all the rocks and smash all the fish bowls that have Mr. Timms. Players can purchase upgrades from Wounded Bird the raven for sheriff stars. Rango cannot purchase the same upgrade all the time, so he must spend the stars wisely. A shotgun acts as a TNT barrel which can blow up all enemies. Going to the golf area makes him fire a bug into the targets and zombies. A squared object can be pushed by him in the games. Bosses are found in all levels, including non-movie characters, such as a giant spike cockroach, charger, brawler and alien probe.
Rango rides a roadrunner to Dirt, while in the movie, he walks all the way.
Roadkill the Armadillo is omitted.
Rango survives through Lars' home.
The citizens celebrate Dirt when Rango destroys the aliens, while in the movie, he brings the water back for all the citizens of dirt.
Ambrose did not appear in the game, but he appeared on the case.
Rango saves Beans from Bad Bill from the stage coach.
Rango kills Rattlesnake Jake in his town, while in the movie, Rattlesnake Jake starts to attack Tortoise John.
The vicious angry hawk is omitted.
Tortoise John is the only villain to never appear in the game, along with Balthazaar.
The peccaries are omitted.
Mr. Black warns Rango and Beans to go to the clock tower.
The desert toad killed by the hawk is omitted.