US 43 travels concurrently with Alabama State Route 13 (SR 13) from its southern terminus to an intersection in southeastern Fayette County.

Upon intersecting the Craft Highway in Chickasaw, the roadway adds another lane in each direction.

As it enters Saraland, the highway meets State Route 158 (SR 158), which connects to Interstate 65 (I-65) to the west.

US 43 continues north on a four-lane divided highway that runs roughly parallel to the meandering Mobile River.

A trumpet interchange near Calvert provides access to a steel mill between the highway and the river.

In McIntosh, the highway passes Andrews Chapel, a historic log church.

North of McIntosh, the highway runs through forest land; clearings dot the roadside occasionally.

Roughly halfway between Grove Hill and Thomasville, SR 178 connects Fulton to the highway system.

When the highways reach Providence, the two roads fork and US 43 takes the western leg; SR 69 heads north toward Greensboro.

The two routes head west together for about one mile (1.6 km) before US 43 turns back to the north.

The highway passes by the town square and in between the Tombigbee and Black Warrior Rivers before crossing the latter.

In the middle of town, the two routes meet northbound U.S. Route 11 in Alabama at the Greene County Courthouse Square District; southbound US 11 goes around the other side of the block, effectively making the courthouse square its median.

SR 69 descends from the elevated highway and joins US 43 on Lurleen B. Wallace Parkway through the downtown area and past the historic Bama Theatre.

The northbound and southbound lanes are separated by a block until they join to cross the Black Warrior River on the Hugh R. Thomas Bridge just above the Oliver Dam and then enter Northport.

[5] It crosses over an arm of Lake Tuscaloosa and travels along the western edge of Binion Creek Landing Park.

Approximately 2,000 feet (610 m) after crossing the Sipsey River the highways enter Fayette where they intersect SR 171 (2nd Avenue Southeast) in the downtown area.

Then, they cross over the Tennessee River on the O'Neal Bridge and enter Lauderdale County.

The highways pass near University of North Alabama's main campus and travel to the northeast.

They continue to the north and east until they reach the Tennessee state line, where SR 13 ends.

The highway begins a curve to the north, crossing the South Fork of the Buffalo River.

After that junction, it passes by Stillhouse Hollow Falls, a Class I Scenic-Recreational State Natural Area (https://www.tn.gov/environment/program-areas/na-natural-areas/natural-areas-middle-region/middle-region/na-na-stillhouse-hollow-falls.html) The highway continues over Big Bigby Creek and to the junction with the North end of Lawrenceburg Highway.

It intersects the southern terminus of SR 243 (South Main Street) in Mount Pleasant.

At an interchange with SR 50 (Williamsport Pike), the concurrency briefly re-enters the city before leaving again.

Here, US 43 ends, US 412 continues to the east-southeast on Bear Creek Pike, and SR 6 turns onto US 31 north.

[8] Prior to the completion of Corridor X in western Alabama, US 43 and US 278 shared a concurrency with US 78 between Guin and Hamilton.

In 1934 as part of a proposal to eliminate the US 31W and US 31E spilt, US 43 was to be extended north to Hopkinsville, Kentucky on US 31 and modern day US 41A.

The project is expected to help the economies of cities in the Black Belt by connecting communities in western Alabama, the Port of Mobile, I-65, and I-20/I-59.