One route of 53.31 miles (85.79 km) begins at the Louisiana state line and runs north to US Highway 371 (US 371) south of Prescott.

Both routes are maintained by the Arkansas State Highway and Transportation Department (AHTD).

The route was extended from Gurdon north to Holly Grove on July 10, 1957, adding 11 miles (18 km).

[8] A third section of Highway 53 was created in Lafayette County between the Louisiana state line and McKamie on March 7, 1961.

[9][10] The gap between the two southern routes was closed two years later when Highway 53 was extended north from McKamie to US 82 Truck in Stamps on June 23, 1965.