[1] The stream headwaters arise in northern Gray County, Texas at 35°36′29″N 100°35′55″W / 35.60806°N 100.59861°W / 35.60806; -100.59861 northeast of Laketon and southeast of Miami at an elevation of 3010 feet.
The stream turns south and southwest to enter the North Fork of the Red River 2.5 miles from the Oklahoma-Texas line.
Along its banks were located favored hunting camps of Plains tribes, such as the Comanche and Kiowa.
The encroachment of American hide hunters at Sweetwater Creek was contested by the Comanche and their Kiowa allies.
[5] The town of Mobeetie, Texas, a Native American word meaning "sweet water", and Sweetwater, Oklahoma, are named for the creek.