The route's northern terminus is in Pine Bluff, Arkansas, at an interchange with Interstate 530/U.S.

US 425 then splits and heads northeast, running concurrently with LA 15 through mostly farmland and small towns.

The route enters Arkansas near Rawls and runs north through rural Ashley County.

In Hamburg, the routes are joined by Highway 8, which runs east and west across the southern part of the state.

[3] North of the junction, the three routes pass the First United Methodist Church and historic properties within the Hamburg Commercial Historic District before US 82 turns east at St. Louis Street and US 425/AR 8 run north out of Hamburg.

Passing more agricultural land, Highway 8 turns west in Fountain Hill just before the Drew County line.

[4] The route now curves to the west side of town, with Main Street (AR 83) serving downtown Monticello.

After AR 35 turns west, Highway 425 has many rural junctions with county routes.

Zion Presbyterian Church in Relfs Bluff and the Parker House before entering Star City.

The route is essentially the same as it was at inception in the 1926 state highway plan, connecting the major cities in its area of southeast Arkansas.

LA 137 was removed from the state highway system in 2005, when US 425 was extended south to Mississippi.