Missouri State Route 221 is a north-south highway in Southern St. Francois County. It runs from U.S. Rt. 67/Missouri Secondary State Route W, at Farmington, to Missouri State Route 21, at Pilot Knob. MO St Rt 221 passes through the following towns in St. Francois County. Farmington Doe Run Pilot Knob MO St Rt 221 is not multi-plexed in St. Francois County. MO St Rt 221 intersects the following highways in St. Francois County. U.S. Rt. 67, at Farmington. Missouri Secondary State Route W, at Farmington. Missouri Secondary State Route B, at Doe Run. Missouri Secondary State Route NN, near Inron Mountain Lake. Missouri State Route 21, at Pilot Knob.
