[2] It heads east into Van Buren, giving access to Fort Smith as well across the Arkansas River to the south.

[5] I-40 runs through Clarksville (where it has a junction with US 64), passes over part of Lake Dardanelle, and meets Highway 7 (AR 7) in Russellville.

[6][7] I-40 continues to the east through Morrilton before turning south to Conway and Faulkner County.

[10] Passing through Lonoke, the route runs through rural Arkansas with straight alignments and relatively few junctions, forming an overlap with US 63 in Hazen until meeting US 49/AR 17 in Brinkley.

[11][12][13] Upon entering St. Francis County, I-40 runs northeast to Forrest City, where it intersects with AR 1.

[15] The highway continues to the northeast to an interchange with I-55, and the two routes form a concurrency east for 3.1 miles (5.0 km).