The river flows for its entire course in central Calumet County. It rises about 3 miles (5 km) east of Lake Winnebago and flows generally east-southeastwardly; it joins the South Branch of the Manitowoc River about 6 miles (10 km) east of Chilton in the Killsnake Wildlife Area.
The 5,777 acres (23.38 km2) surrounding the confluence of the Killsnake River with the South Branch Manitowoc River has been designated a wildlife refuge by the Wisconsin Department of Natural Resources.  The area is located entirely in the town of Rantoul.
There are four archaeological sites ranging from a major Early Paleo-Indian campsite from 9000 BC to a Potawatomi village from the mid-19th century AD located in the wildlife area,  and the site is listed on the National Register of Historic Places.
- U.S. Geological Survey. National Hydrography Dataset high-resolution flowline data. The National Map Archived 2012-04-05 at WebCite, accessed December 19, 2011
- Wildlife areas in Northeast Wisconsin, Wisconsin Department of Natural Resources, Retrieved July 17, 2007
- Wisconsin Natural Resources magazine; April 1999; Retrieved July 17, 2007
- Killsnake Wildlife Area - Wisconsin DNR
- DeLorme (1992). Wisconsin Atlas & Gazetteer. Freeport, Maine: DeLorme. ISBN 0-89933-247-1.
- U.S. Geological Survey Geographic Names Information System: Killsnake River
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