LA 6 is also steeped in history, as it roughly follows the El Camino Real de los Tejas, a National Historic Trail, and passes through Natchitoches, the oldest permanent settlement in the Louisiana Purchase.

[2][3][4] LA 6 enters Many on San Antonio Avenue and intersects US 171, which heads northwest to Zwolle and south to Leesville.

[2][4][5] Continuing northeast into Natchitoches Parish, LA 6 enters the village of Robeline on Texas Street.

[2][4][7] Approaching the main part of town, LA 6 again becomes a divided four-lane highway as it reaches a four-way intersection at the Natchitoches Bypass.

At a T-intersection with Washington Street, LA 6 rejoins the business route and turns north away from town.

[2][4][7] 2.3 miles (3.7 km) later, at a point known as Grand Ecore, LA 6 crosses a beam bridge over the Red River.

Immediately after crossing the Kansas City Southern Railway (KCS) tracks, LA 6 reaches its eastern terminus at a four-way intersection with US 71 and US 84.

LA 6 originally entered Louisiana by crossing the Sabine River on a bridge built in 1937 at the former community of Pendleton, Texas.

The current bridge, much longer in length, was constructed in 1963 when the river became part of the Toledo Bend Reservoir.

Two miles of previously dry land at the western end of LA 6, an area formerly known as East Pendleton, are now under water crossed by the current bridge, which follows a slightly straighter alignment than the old road.

[3][21] Approaching the eastern terminus at Clarence, LA 6 originally crossed the Red River at Grand Ecore on a now-demolished bridge that existed immediately to the east of the current span built in 1959.

turns northward onto Jefferson Street, an undivided two-lane roadway, and enters the Natchitoches Historic District.

intersects LA 494 (Keyser Avenue), which traverses the eastern part of town on the opposite bank.

Entering the downtown area, the roadway maintains a brick surface in keeping with its historic surroundings.

Leaving the downtown area, LA 6 makes a slight jog onto Washington Street where it regains its modern road surface.