Just a few miles into the state, the two highways run on the eastern edge of El Dorado as an expressway.

In Mammoth Spring, US 63 crosses into Missouri, traveling to West Plains.Portions of U.S. 63 in northern Arkansas have their origins in the work of the Ozark Trails Association, which established a network of roads in northern Arkansas and southern Missouri beginning in the 1910s.

A portion of roadway was mapped out in Arkansas between Mammoth Spring and Memphis, Tennessee, and built c. 1918-22.

Some of the original infrastructure of this early construction has survived the 1927 Mississippi flood and the realignment of U.S. 63 in 1967.

Northwest of Tyronza, Old U.S. 63 runs for about 1-1/4 miles of original concrete pavement;[1] it was listed on the National Register of Historic Places in 2009.

[6] However, a small section of US 63 in Jonesboro was redesignated as I-555 on November 23 of the same year, making US 63 partly concurrent with I-555 again.