Determined as an important alternate route to congestion-plagued Highway 371, this road has been designated a Minnesota Regional Corridor along its entire length.

State Highway 64 serves as a north–south route in north-central Minnesota between Motley, Akeley, and Hendrickson Township.

The part of the route from Akeley to State Highway 200 was authorized in 1949, but not constructed until the mid-1960s.

The section of the route between Akeley and Highway 200 was built as a new road by 1965.

A sharp 90 degree turn along this stretch was smoothed out, and the road widened through a swampy area that had steep dropoffs on either side leading to water-filled ditches.