State Highway 65 begins at US-70 12 miles (19 km) east of Randlett in Cotton County.

The two highways head east through town on Oregon Street before reaching Commercial Avenue, where SH-5 splits off to the south and SH-65 turns north.

SH-65 continues north on Commercial for three blocks, then makes a right turn to head east on Boundary Street.

Originally, SH-65 began at the Red River as a continuation of TX-148 and extended north to Walters, using the present-day routes of SH-5B, a small section of SH-5A, and SH-5.

The non-concurrent sections of the former SH-65 routing north of US-70 were dropped from the state highway system, excepting the portion from Elgin to Sterling, which became a western extension of SH-17.

A section of dirt road between US-70 and Temple had been also added to SH-65 by June 1944, setting the highway at its present-day termini.