State Trunk Highway 161 (often called Highway 161, STH-161 or WIS 161) is a 22.42-mile (36.08 km) state highway in Portage and Waupaca counties in the central part of the US state of Wisconsin.

It runs in east–west from US Highway 10 (US 10) northwest of Amherst Junction via Iola to WIS 22/WIS 110 just west of Symco.

Starting at US 10 between Custer and Amherst Junction, WIS 161 begins to proceed eastward.

As a result, WIS 161 extended west to US 10's new alignment.

WIS 161's former connection was then transferred to local control (replaced by CTH-A, now CTH-Q).