It travels northward through northeast Arkansas, connecting the cities of West Memphis and Blytheville.

For the majority of its routing through Arkansas, I-55 generally follows U.S. Highway 61 (US 61) and has a 67.08-mile (107.95 km) long concurrency with US 78 from the Tennessee state line in Memphis to Blytheville for most of its length.

In Turrell, I-55/US 61/US 78 meets the southern terminus of I-555, a spur route of I-55 connecting Jonesboro to the Interstate Highway System.

Slightly east of this junction, these frontage roads depart I-55/US 78, with AR 77 running near Birdsong and US 61 serving Wilson.

[3] I-55/US 78 continues northeast, intersecting minor state highways in rural Mississippi County before a junction with US 61 in south Blytheville.