US 425/LA 15 travels along a widely spaced four-lane one-way pair through town en route to its immediate destinations of Ferriday and Sicily Island.

One block after crossing the Kansas City Southern Railway (KCS) line, the route intersects US 80 (East Green Street), which serves local traffic along the I-20 corridor.

The travel lanes of US 65 converge as the highway heads out of Tallulah and begins to follow alongside the Delta Southern Railroad (DSRR) tracks.

Departing from the lake shore, US 65 curves due north and rejoins the straight alignment of the DSRR tracks for its final 10 miles (16 km) in Louisiana.

[3][8][9] US 65 alternates between a rural and urban principal arterial over the course of its route, as determined by the Louisiana Department of Transportation and Development (La DOTD).

[13] Known as the Scenic Highway, it paralleled the west bank of the Mississippi River through the northeastern portion of the state and served as an important connection between the capital cities of Louisiana and Arkansas.

This change extended US 65 a distance of 187 miles (301 km) and allowed motorists to follow a single highway number from New Orleans to Little Rock, Arkansas.

[16][17] It came three years after US 61 was almost entirely relocated between New Orleans and Baton Rouge from its original path alongside the winding Mississippi River onto the modern, streamlined Airline Highway.

By 1930, the perceived lack of initiative in fulfilling this promise drew much criticism from the pair's political opponents based in northeastern Louisiana.

[22][23] However, in October of that year, bidding was opened for 31 contracts in the "largest letting for road and bridge construction in the history of the state" up to that time.

[24] This included the paving of an 11-mile (18 km) stretch of US 65 in East Carroll Parish between Lake Providence and Transylvania that was completed the following year.

[30] The bridge's construction was primarily advanced by the state of Mississippi and the local governments of Adams County and the city of Natchez.

Under this arrangement, the Louisiana Legislature aided the project by passing a special bill in June 1938 allowing the bridge to be exempt from state taxes.

[37][38] The cantilevered through truss structure was designed by the engineering firm of Ash, Howard and Needles, which had been responsible for the US 80 bridge at Vicksburg a decade earlier.

[40] While the Natchez–Vidalia Bridge was under construction, virtually the entire town of Vidalia consisting of about 1,000 citizens, was demolished and rebuilt several blocks away from the river bank.

This allowed for the construction of a setback levee that would enable the widening of the river at Natchez and reduce the pressure of the current on its banks, which was cited as a great hazard to both towns.

[41] Between about 1949 and 1962, virtually the entire route of US 65 was relocated onto a streamlined alignment south of Tallulah, often following the now-abandoned Missouri Pacific Railroad line.

[20][42] In 1953, US 65 was straightened through the Newellton area, moving the route slightly outside of the town and bypassing another section of the current LA 605 along the shore of Lake St.

Each bridge then began to carry two lanes of traffic, creating a four-lane highway crossing of the Mississippi River at Natchez.

[52] The only major change to US 65 since this time occurred when US 425 was extended from Bastrop, Louisiana to Natchez, Mississippi largely over the existing alignment of LA 15.

[c] The route followed the recently constructed Airline Highway around what was then the outside of town, allowing through traffic from the south and east to access the Mississippi River Bridge while avoiding the downtown area.

Directly east of the downtown area, the route intersected US 190 (Florida Boulevard) at a traffic circle that has since been replaced by a cloverleaf interchange.

With mainline US 190 heading west directly into Downtown Baton Rouge, Airline Highway continued northwest as US 61/65/190 Byp.