Route 181 is a highway in southern Missouri. Its northern terminus is at Business U.S. Route 60 in Cabool; its southern terminus is at U.S. Route 160 in Gainesville.

The road intersects with Route 14 near the twin bridges. It runs concurrently with Route 14 westward for about 1-mile (1.6 km), then heads back south toward Dora. About three miles (5 km) south of Dora, near Highway CC, Route 181 heads west again toward the Hodgson and Zanoni mills, while Highway H continues southward toward US 160.