One of the early stops on the Overland Stage Route and the Pony Express, Green River was incorporated in 1868 as part of the Dakota Territory. Near downtown Green River is Expedition Island (a National Historic Site), the place where John Wesley Powell began his famous expeditions down the Green River, the Colorado River and then through the Grand Canyon. At the time of incorporation, Green River had about 2,000 residents and a number of permanent adobe buildings were under construction. However, when the Union Pacific Railroad arrived, the railroad brass discovered a town where they wanted to set up a division point. Because the town was already in place, they couldn't just plat out their own town, sell off the land and control all the business in the area. So they moved the division point 12 miles to the west. Green River almost dried up and blew away with the population dropping to 101. Then the Black Fork (at the new railroad division point) dried up during a drought and the Union Pacific was forced to move the division point back to Green River. Green River was incorporated again under the new laws of Wyoming in 1891 and is the county seat of Sweetwater County.

Green River is at one of the entrances to the Wild Horse Loop, a driving tour across the prairie where 3,500 wild horses still roam. Also in town is the Sweetwater County Historical Museum, which showcases both the geology and the human history of the area with a special focus on the trails, railroads and mines of the area. In the summer, Green River is the scene for the Flaming Gorge Days, River Festival and the Overland Stage Stampede Rodeo.

The Green River Basin contains the world's largest known deposit of trona ore (a source of sodium bicarbonate) and there are 5 major mines in the area. The Basin also contains large reserves of natural gas and oil shale. That means that in this day of ridiculous fuel prices, Green River and Rock Springs are booming with the renewed emphasis on domestic oil and gas production.

The city of Green River lies about 15 minutes drive north of Flaming Gorge Reservoir and the Flaming Gorge National Recreation Area, via the Flaming Gorge-Green River Basin Scenic Byway. Green River is also one of the first cities in the US to ban door-to-door solicitation.