| State: | MO |
| Type: | MO |
| Route: | 81 |
| Map Custom: | yes |
| Map Notes: | Route 81 highlighted in red |
| Length Mi: | 40.954 |
| Direction B: | North |
| Direction A: | South |
| Terminus B: | near Farmington, IA |
| Terminus A: | west of Canton |
| Junction: | south of Kahoka |
| Previous Type: | MO |
| Previous Route: | 80 |
| Next Type: | MO |
| Next Route: | 82 |
Route 81 is a highway in northeastern Missouri. Its northern terminus is at the Iowa state line where it continues as Iowa Highway 81. Its southern terminus is at Route 16 west of Canton.
Route 81 starts at the Iowa state line from Iowa Route 81. It continues south into the town of Kahoka and then intersects with US Route 136. As it continues south, there are several sharp turns. It ends outside of the town Canton, near an interchange with US 61 and intersects with Route 16. The route starts in Clark county and ends in Lewis county.