US 43, along with unsigned SR 13 which is concurrent with it, begins at an interchange with US 90 (New Bay Bridge Road; unsigned SR 16) in the extreme southeastern corner of Prichard, in Mobile County. It travels to the north-northwest and leaves Prichard and travels through a brief section of Mobile. The highway crosses over some railroad tracks and enters Chickasaw. It curves to the north and curves to the north-northeast. It then crosses over Chickasaw Creek on the R.B. Smallwood Sr. Memorial Bridge. Not long after, US 43 leaves Chickasaw and enters Saraland. It has an intersection with the eastern terminus of SR 158 (Industrial Parkway). It crosses over Norton Creek and intersects the northern terminus of SR 213 (Shelton Beach Road). A few thousand feet later, the highway enters Satsuma. It passes Satsuma High School and Satsuma Lions Park before crossing over Steele Creek. It curves to the north-northwest and has an interchange with Interstate 65 (I-65) at exit 19. US 43 leaves Satsuma and curves back to the north-northeast. It then travels through Creola. The highway then travels through Axis and curves to the north-northwest. The highway curves to the north and travels through Le Moyne. It intersects the eastern terminus of County Route 84 (CR 84; Salco Road). After crossing over Sisters Creek, the highway travels through Barry Village and Bucks. It crosses over Grady Hall Creek and travels through Chastang. It travels through Movico, the highway curves to the north-northeast and crosses over Cedar Creek. Almost immediately, it enters Mount Vernon. There, it intersects the eastern terminus of CR 96 (Citronelle Road). It curves to the north and crosses over Beaver Dam Creek before leaving Mount Vernon. The highway crosses over Borrow Creek and then has an interchange with ThyssenKrupp Drive. It enters the southern part of Calvert. While in the center part of Calvert, it crosses into Washington County.