[2] From its southern terminus in Iowa at US 90 (near Lake Charles), US 165 follows a diagonal north south route, passing through the casino town of Kinder, where it intersects US 190.

Just south of Alexandria it merges with US 71 and they join through the west side of the city, across the Red River and into Pineville.

Due to the Louisiana DOT TIMED Project, US 165 is now a four lane divided highway from Iowa to Bastrop.

US 165 continues north near Cut-off Creek Wildlife Management Area to enter Drew County.

[6] The route forms a concurrency north with Highway 1 for 24.99 miles (40.22 km) beginning at Back Gate.

Upon entering Arkansas County, the route passes the A.M. Bohnert Rice Plantation Pump#2 Engine and through sectioned farmland before meeting US 165B in Gillett.

[7] US 165/AR 1 continue north to De Witt, with AR 1 breaking east and US 165 turning due west.

US 165 skirts the eastern edge of the city as Park Avenue before it turns west to intersect US 63 and enter Prairie County.

Established in 1938, the route is actually a series of roads which connect Canada and the Gulf of Mexico along the Mississippi River.

The portion of US 165 from the beginning of its concurrency with US 65 near Dermott north to De Witt is part of the Great River Road in Arkansas.

Some of this original pavement has been preserved by the National Register of Historic Places as Old AR 11 – Kauffman Road.

US 165 Business travels north while meeting LA 180, a former segment of the Jefferson Highway auto trail, and crossing the Pineville Expressway before ending at an intersection with its parent route.

[13] The route serves mostly as Front Street and passes near the Old Gillett Jail on the National Register of Historic Places.