Less than ten years after Major Powell's pioneering voyage, the first permanent settlement in the Utah's Green River drainage was founded. Vernal was settled by a party of Mormons led by Jeremiah Hatch in 1878. Despite a hard winter, when a number of the settlers died during a diphtheria epidemic, and an Indian scare caused by the Meeker Massacre in Colorado, Vernal survived and is today the largest town in the Green River Basin. Jensen, a town sited on the river twelve miles east of Vernal, was founded at the same time. A few years later, near the old Spanish Crossing (also known as Gunnison's Crossing), the town of Blake was founded by construction crews of the Denver and Rio Grande Western Railway. In the late nineteenth century, the town of Green River, Utah, was founded across the river from Blake; the two towns have since grown together and are known by the name Green River. The vast majority of the land found in the Green River basin is controlled by the federal government; private lands are largely limited to bottoms along the river itself, used for agriculture, and to townsites. In addition, the Uintah-Ouray Ute Indian Reservation is located on either side of the river from below Jensen to just above Green River, Utah.
There have been no gold or silver rushes into the Green River basin in Utah; until World War II, the major source of income in the area was farming and ranching. Shortly after that conflict, however, a producing oil well was developed in the Ashley field, east of Vernal, and oil and gas production have since become a major source of income for the residents of the Green River basin. The other major source of mineral wealth found in the Green River basin is coal, which is mined extensively in the drainage of the Price River, a minor tributary of the Green. As with any mineral-extraction-based economy, this has resulted in a boom-and-bust cycle that affects residents of the Green River basin to this day.