It runs 64.7 miles (104.1 km) west-to-east through Woods, Alfalfa and Garfield counties.

The first 12 miles (19 km) of SH-45 heading east out of Waynoka is concurrent with US-281.

SH-58 joins SH-43 for a one-mile (1.6 km) concurrency just south of the town of Helena, and at Goltry, SH-45 jogs south a few miles before turning back to the east and heading for a brief concurrency with SH-132 at Carrier.

Continuing to the east, SH-45 travels eight more miles (12.9 km) from Carrier, before reaching its terminus at US-60/64/81 at the north edge of Enid.

[5] In either 1971 or 1972, the highway was extended eastward to its present terminus on the northern outskirts of Enid.