The western terminus of SR 265 is at its junction with US 40 approximately 2.50 miles (4.02 km) east of the city limits of Cambridge.

The highway's eastern terminus is at a T-intersection with SR 147 nearly 3 miles (4.8 km) southwest of Barnesville.

The NHS is a system of routes determined to be most important for the economy, mobility and defense of the nation.

The designation was applied to a stretch of roadway that was formerly a portion of SR 148.

It has maintained the same routing through portions of Guernsey, Noble and Belmont Counties throughout its history.