Antelope Creek starts where its east and west forks join, northwest of Panhandle in northwestern Carson County (at 35°35' N, 101°32' W), and flows north through a ranching and oil area for twelve miles to its mouth on the Canadian River, east of Sanford in southwestern Hutchinson County (at 35°44' N, 101°29' W). The stream was once a part of the LX Ranch. It gave its name to the Antelope Creek Focus, the common term used by archeologists for sites of pre-Columbian Indian slab-house ruins in the general area. The stream crosses an area of rolling to steeply sloping terrain and loamy and clayey soils. The vegetation includes juniper, cacti, and sparse grasses.