The route traverses the rural pine forests in three of the state's Florida Parishes, crossing three rivers along the way: the Tickfaw, Tangipahoa, and Bogue Chitto.

The undivided two-lane highway briefly heads northeast to Chipola, intersecting LA 432, then turns due east to Easleyville.

[2][3][4] LA 38 enters the town of Kentwood and becomes known locally as Avenue G. The highway passes through a diamond interchange with I-55 at exit 61, connecting with Hammond, Louisiana to the south and Jackson, Mississippi to the north.

Widening to an undivided four-lane highway, LA 38 serves as the town's primary east–west thoroughfare and passes a number of small businesses.

Narrowing back to two lanes, LA 38 crosses the parallel Canadian National Railway (CN) line at grade and exits the town at the first of several small bridges over the Tangipahoa River and its tributaries.

Over the next 6.5 miles (10.5 km), the highway gradually resumes its eastward course before crossing the sandy beaches of the Bogue Chitto River.

The portion between the Tangipahoa River and the Washington Parish line was completed in 1949, along with two small segments through Mount Hermon and Clifton.

The western and eastern ends of the modern LA 38 have a convoluted history due to the early practices of highway numbering in Louisiana.

The western portion between Coleman Town and Chipola, connecting the route to what is now LA 10, was added to the state highway system in 1928.

[8][20] Meanwhile, the eastern segment of the modern LA 38 extending from Clifton to south of Hackley was originally part of State Route 262, another addition to the system in 1928.

[26][27] The only change to the route of LA 38 since its creation involved the elimination of a zigzag at the Illinois Central Railroad (now Canadian National Railway) crossing in Kentwood.