A city torn apart by numerous gang wars is in a volatile state and normal everyday people get caught in the middle. You would have been a victim of the chaos on the streets, had it not been for Julius, the leader of the 3rd Street Saints, you’d have just been another statistic. Julius invites you to join them and unite the city under the 3rd Street Saints. With little doubt the rest of the feuding gangs will bring the city to its knees, you join him. However, you quickly realize that the major three gangs, the Westside Rollerz, Vice Kings, and Los Carnales aren't going to be easy to uproot at all.

Saints Row is an open world driving and action game similar to Grand Theft Auto series. In the beginning of the game the player can customize the physical characteristics of the protagonist. The player then proceeds to do missions against any of the game's three gangs to advance the overall story, perform activities that range from stealing prostitutes to committing insurance fraud or becoming a hitman, or simply roam the city freely.

Fighting opposing gangs occupies the largest portion of the game. The Westside Rollerz are lead by Joseph Price and specialize in street racing and anything to do with cars; the Vice Kings are lead by the entrepreneur Benjamin King and are into prostitution, retail, and recording studios; Los Carnales are lead by Hector 'Kimo' Lopez and specialize in drug trafficking. The player character can get help from his gang members, who can provide backup in fights. Cars can be upgraded with body and performance enhancing kits. The game also features twelve radio stations to listen to.

It is possible to play with up to twelve people online in either co-op, deathmatch, team deathmatch, Big ass Chains (a mode where chains are collected by killing players for points), Protect the Pimp (where one team has a pimp and must keep him from getting killed by the other team), and Blinged Out Ride (where each team must collect chains to bling out their ride several times).