Missouri Route 221
# Missouri Route 221

Route 221 is a 16.317-mile-long (26.260 km) east–west highway in eastern Missouri. Its western terminus is at Route 21 near Pilot Knob. Its eastern terminus is at U.S. Route 67 (US 67) near Farmington.

## Major intersections

| County | Location | mi | km | Destinations | Notes |
| - | - | - | - | - | - |
| Iron | ​ | 0.000 | 0.000 | Route 21 | |
| St. Francois | ​ | 9.040 | 14.548 | Route NN | |
| St. Francois | Doe Run | 12.744 | 20.509 | Route B | |
| St. Francois | ​ | 16.140– 16.317 | 25.975– 26.260 | US 67 / Route W | Diverging diamond interchange, existing interchange converted September 2012 |
| 1.000 mi = 1.609 km; 1.000 km = 0.621 mi ||||||
