Since then, US-59 has undergone only minor adjustments, many of which eliminated curves and provided a more direct route for travelers using the highway to traverse eastern Oklahoma.

US-59 enters Oklahoma in Le Flore County, in the Ouachita National Forest, at the state line at Fogel, Arkansas.

US-59 and US-270 head north, paralleling the Black Fork Poteau River as they leave the national forest, into Hodgen.

North of Hodgen, the highways cross the main branch of the Poteau River and pass through the Wister Wildlife Management Area.

[4] Upon landing on the north bank of the river, US-59 and US-270 curve to the northeast as they enter Heavener, where SH-128 terminates.

It crosses the Arkansas River on a bridge just downstream of the dam that impounds Robert S. Kerr Reservoir.

US-59 continues northward, crossing Wildhorse Mountain as well as Little Sallisaw Creek, just upstream of where it empties into Robert S. Kerr Reservoir.

The route continues to follow a winding course as it makes its way northeast to unincorporated Cherry Tree.

The highway continues northeast past Cherry Tree, before turning back to a due north course as it makes its way into the county seat of Stilwell.

[3] US-59 leaves Stilwell, twisting through mountainous terrain alongside Peavine Creek until the stream's mouth at the Baron Fork of the Illinois River.

[5] In northern Adair County, US-59 serves unincorporated Ballard and the town of Watts, where it runs just west of Lake Frances.

North of Watts, the highway crosses the Illinois River and continues northward into Delaware County.

[5] The two highways enter Kansas, Oklahoma, where they part ways at an intersection with SH-10; US-412 Alternate continues to the east, while US-59 turns north along SH-10.

However, only 0.8 miles (1.3 km) northeast of the junction, US-60 splits off at a cloverleaf interchange which also provides access to I-44, the Will Rogers Turnpike.

[8] Before US-59 was designated in Oklahoma, what would become its route was designated as US-270 between the Arkansas state line and Poteau, US-271 between Poteau and Sunset Corner, SH-10 along the modern-day SH-9 concurrency, SH-17 between Sallisaw and West Siloam Springs, SH-33 between West Siloam Springs and the town of Kansas, and SH-10 between Kansas and Grove.

At this time, the road south of Sallisaw was marked as "Conditional Location", and between Grove and the Kansas state line, the highway followed a different route: it proceeded west out of Grove to meet US-60 / US-66 south of Afton, concurring with those two highways to Vinita, where it turned north along SH-2, following it to Welch and the state line.

[16] On July 6, 1964, the Oklahoma State Highway Commission approved a realignment to US-59's route through Poteau.

This moved US-59 onto a new bridge over the Arkansas River upon completion of its construction, with the old highway being turned over to the U.S. Army Corps of Engineers.

An application for this change was received by the American Association of State Highway Officials (AASHO) on March 26, 1968, and approved by that body on June 18, 1968.

On that date, the commission approved a realignment of US-59 from a point south of the intersection with US-270 and US-271, to that junction, and on into Poteau.

[22] The next change to US-59 came on November 2, 1981, when the transportation commission approved moving just over 5+1⁄2 miles (8.9 km) of highway between Flint and West Siloam Springs to the north of the previous alignment.

[25] On March 3, 2003, the commission approved elimination of two sharp curves in western Ottawa County, shortening the highway by 0.57 miles (0.92 km).

[26] The section of US-59 between I-40 and SH-9 was pressed into service as a detour for eastbound I-40 traffic after the collapse of its bridge over the Arkansas River on May 26, 2002.