The Horse Creek subbasin lies within the southern portion of Goshen County, the northern portion of Laramie County, the southeastern corner of Platte County, and a small portion of Albany County. Interstate Route I-25 runs north and south through the western portion of the Horse Creek subbasin, and U.S. Route 85 runs north and south through the eastern portion of the subbasin. State Routes 313 and 151 also service the subbasin.