A second route of 13.87 miles (22.32 km) begins at Airport Road and runs north to Highway 358.

The route runs due north to a skewed intersection with US 63B before terminating at Highway 18.

[3] Between US 49/Highway 1 western junction and County Road 766, the route is part of the Crowley's Ridge Parkway, a National Scenic Byway.

[4] Two Civil War Trail designations follow Highway 351 between Jonesboro and Highway 358; the Steele's Movements trail during the Second Phase Pea Ridge Campaign, and the Davidson's Approach during the Little Rock Campaign.

Both designations represent Highway 351's historic prominence as a main north-south route between Paragould and Jonesboro.