Years after taking Stilwater for their own, the Third Street Saints have evolved from street gang to household brand name, with Saints sneakers, Saints energy drinks and Johnny Gat bobblehead dolls all available at a store near you. The Saints are kings of Stilwater, but their celebrity status has not gone unnoticed. The Syndicate, a legendary criminal fraternity with pawns in play all over the globe, has turned its eye on the Saints and demands tribute.

Refusing to kneel to the Syndicate, you take the fight to Steelport, a once-proud metropolis reduced to a struggling city of sin under Syndicate control. Take a tank skydiving, call in a satellite-targeted airstrike on a Mexican wrestling gang, and defend yourself against a highly-trained military force using only a sex toy in the most outlandish gameplay scenarios ever seen, igniting a city-wide war that will set Steelport on fire.