Created on July 1, 1931 across central Mississippi and southern Arkansas, US 82 eventually became a 1,625-mile-long (2,615 km) route extending from the White Sands of New Mexico to Georgia's Atlantic coast.

The road then traverses the New Mexico villages of High Rolls, Cloudcroft, and Mayhill After descending the mountains into the rugged, flat plains of eastern New Mexico, it generally follows a north-northeasterly bearing until Artesia, where it takes a more due-easterly bearing on through to Lovington, veering back slightly to the north before crossing into Texas.

It once again merges with US 62 (along with State Highway 114) east of the campus of Texas Tech University, where it continues eastward through Ralls, where US 62 makes a sharp turn to the north and leaves the route.

US 82 continues eastward across the level plains of the Llano Estacado to Crosbyton and then dips downward as it crosses the White River of Blanco Canyon, where the Texas Department of Transportation maintains the Silver Falls Rest Area with facilities and hiking trails.

After climbing out of Blanco Canyon, US 82 eventually exits the Llano Estacado and enters the rolling plains near Dickens, Texas.

US 82 leaves US 287 at Henrietta and continues east, signed independently (apart from various state highway routes) across the remainder of Texas, crossing into Arkansas in downtown Texarkana.

[2] US 82 enters Arkansas in downtown Texarkana, then proceeds almost due east across the flat plains of the Red River.

[3] The new road will commence at the recently opened Mississippi River Bridge and terminate at the current U.S. 82 near Leland, creating a half-loop freeway around South Greenville.

The highway enters the state east of Columbus, Mississippi, and bears southeast towards Northport and Tuscaloosa, where it crosses over I-20 and I-59 south of town.

This approximately 92-mile (148 km) drive goes through some of the most rural areas of the state, much of it two lanes with the exception of the section from Tuscaloosa to Centreville.

New bridges are being constructed using Federal Highway Administration monies, as well as matching Alabama Department of Transportation funds.

[1] The Mississippi Highway Department requested the creation of a route between Greenville and Columbus, additionally proposing that it should be extended eastward to Birmingham, Alabama, and into Arkansas.

New Mexico decided to delete an overlap with US 70 between Alamogordo and Las Cruces, resulting in the current western terminus at US 54/US 70.