It runs east–west in southeastern Wisconsin between Albion and Palmyra, Jefferson County.

Starting at WIS 73 near Albion, WIS 106 proceeds to travel eastward near the north shore of Lake Koshkonong.

Along the way towards Fort Atkinson, it then travels along the north bank of the Rock River.

In Fort Atkinson, it intersects US 12 and Bus.

After that, it continues to travel eastward and then southeastward to Palmyra, meeting Hebron along the way.