Kentucky Route 645 (KY 645) is a 14.692-mile-long (23.644 km) state highway in eastern Kentucky that runs from U.S. Route 23 (US 23) northeast of Ulysses to, temporarily, a dead end east of KY 40 southeast of Inez.

KY 645 was designated on March 22, 1984.

The original KY 645 ran from US 460 in Sideview west via Chiles Highway to Donaldson Road.

The road was given to Montgomery County by September 26, 1980.

An extension of the highway is planned east of KY 40 to Warfield.