From its original termini of Davis and Durant, the route was extended to both the east and the west, reaching its greatest extent in 1933, connecting Duncan to the Texas state line at the Red River.

In 1941, the portion of SH-22 west of Ravia was dropped, and the highway's eastern terminus was set in 1956.

SH-22 turns roughly southeast and continues for 13 miles (21 km) to its second concurrency with SH-78 at Nida (unincorporated).

From Caddo, SH-22 travels east, then south, for 13 miles (21 km) to its terminus at US-70 in Bokchito, in eastern Bryan County.

5 and 6, via Milburn, Tishomingo, Ravia, Mill Creek, Sulphur, and Davis, to a connection with State Highway No.

[3][6] On December 17, 1934, the highway was rerouted over a stretch of Farm-to-Market road between Tishomingo and Nida, bypassing Milburn.