A route between Arkansas City and Rohwer held the Highway 81 designation between 1926 and 1929.

The designation was reused in 1945 to replace Highway 13 between Louisiana and US 65 east of Pine Bluff (present-day US 425).

The route begins at an intersection with US 65 and the northern terminus of US 425 just east of Pine Bluff.

[1] The highway was extended north (along its current routing) to an International Paper plant on February 20, 1957.

[6] Other than a realignment for a bypass in Monticello in 1960,[7] the route remained unchanged until November 16, 1988, when the AHTD and the Louisiana Department of Transportation and Development (LADOTD) proposed supplanting Highway 81 and Louisiana Highway 139 with a new route, US 425.