In its northern portion, it is in the Driftless Area, a region of North America that remained free from ice during the last ice age. Certain parcels contained within the refuge were later transferred to the Driftless Area National Wildlife Refuge.
The refuge is one of only two that spans portions of four states (the other is Silvio O. Conte National Fish and Wildlife Refuge). As of 30 September 2007 the area per state was: Wisconsin: 89,637.54 acres (362.75 km2), Iowa: 51,147.78 acres (206.99 km2), Minnesota: 33,868.64 acres (137.06 km2), Illinois: 33,489.57 acres (135.53 km2).[4]
The following counties border on or have land within the Upper Mississippi River National Wildlife and Fish Refuge. In each state, the counties are listed from north to south. The lakes and rivers within the refuge area of each county are also listed.