From Anniston, US 431 heads northwards towards Gadsden. In East Gadsden, it combines with U.S. Route 278; the combined route passes westward through Gadsden and Attalla before splitting just northwest of Attalla. This route is named Meighan Boulevard in Gadsden and Fifth Avenue in Attalla until reaching US 11. In downtown Attalla, the route shares a brief wrong-way concurrency with US 11. West of Attalla, US 431 again turns to the northwest. At Guntersville, it joins with Alabama State Route 79. Through downtown Guntersville the route is divided into two separate one-way streets; the northbound street is named Blount Avenue, and the southbound street is Gunter Avenue. At the northern edge of Guntersville, the split streets combine and the joint route crosses the Tennessee River via the George S. Houston Bridge, before US 431 splits off and again heads in a northwest direction.