The following highways are numbered 221:
Canada Manitoba Provincial Road 221 Newfoundland and Labrador Route 221 Nova Scotia Route 221 Prince Edward Island Route 221 Quebec Route 221 Saskatchewan Highway 221
China China National Highway 221
Cuba
Santa Clara–Sagua Road (4–221)
Costa Rica National Route 221
Japan Japan National Route 221
United Kingdom road B221 road
United States U.S. Route 221 Alabama State Route 221 Arkansas Highway 221 California State Route 221 Florida State Road 221 (former) Georgia State Route 221 (former) Iowa Highway 221 (former) K-221 (Kansas highway) (former) Kentucky Route 221 Maine State Route 221 Minnesota State Highway 221 (former) Montana Secondary Highway 221 Nevada State Route 221 New Mexico State Road 221 New York State Route 221 Ohio State Route 221 Oregon Route 221 Pennsylvania Route 221 Tennessee State Route 221 Texas State Highway 221 (former) Texas State Highway Loop 221 (former) Utah State Route 221 (former) Washington State Route 221 Wyoming Highway 221