Its northern terminus is at the Michigan state line just 0.25 miles (0.40 km) north of the village limits of Metamora.

Continuing north into Michigan's Lenawee County is county-maintained Loar Highway.

The NHS is a network of highways identified as being most important for the economy, mobility and defense of the country.

[4][5] The only significant change to take place to the routing of SR 64 was an extension at the southern end that happened in 1969.

Coinciding with the completions of both I-75 on the east side of Bowling Green, and the U.S. Route 6 (US 6) bypass of the city to the south, SR 64 was extended east from the present SR 25 (former US 25) intersection in downtown Bowling Green along the former routing of US 6 on Main Street to its present southern terminus at the junction of I-75 and SR 105.