The route connects a string of small towns and cities across the Central Louisiana, Acadiana, and Florida Parishes regions of the state.

The western terminus in Vernon Parish comes within 15 miles (24 km) of reaching the Sabine River at the Texas state line and making LA 10 a true cross-state route.

Passing through the commercial section of town, the highway crosses the Acadiana Railway (AKDN) tracks and intersects LA 29 (South Chataignier Street).

Shortly afterward, the one-way couplet ends as US 167 and LA 10 proceed eastward out of Ville Platte as an undivided four-lane highway with center turning lane once again.

Just outside the city limits, the highway narrows to two lanes and then curves to the southeast at LA 748 (Grand Prairie Road) en route to the St. Landry Parish line.

[2][9][11] The route resumes as a gravel road on the east bank of the Atchafalaya River in an area of Pointe Coupee Parish known as Red Cross.

The route follows alongside Bayou Fordoche as it bends to the east toward the village of Morganza, located on the west bank of the Mississippi River.

LA 10 proceeds eastward for 4.4 miles (7.1 km), traveling over a railroad overpass, to the foot of the John James Audubon Bridge over the Mississippi River.

LA 10 widens to a divided four-lane highway as it follows the cable-stayed bridge across the river and crosses into West Feliciana Parish.

[12][13][14] LA 10 returns to grade after 2.3 miles (3.7 km) as an undivided two-lane highway and curves to the northeast through a rural and forested area.

At the eastern edge of town is an intersection with LA 68 (Carrs Creek Road), connecting to Wilson on the north and Baton Rouge via US 61 on the south.

3.2 miles (5.1 km) east of Jackson, LA 10 crosses over the Gloster Southern Railroad (GLSR) line at a point known as McManus.

The highway passes between a residential development and a large tract of open land shortly before intersecting LA 955, which heads south through Grays to a point near Slaughter.

[12][17][18] Shortly after crossing into Tangipahoa Parish, LA 10 passes through an interchange with I-55 at Exit 53, connecting to Hammond on the south and Jackson, Mississippi on the north.

Proceeding due east, LA 10 intersects US 51 at Fluker and turns south to follow that highway, running parallel to the Canadian National Railway (CNRR) tracks.

The latter junction is located in an area known as Wilmer, and LA 10 continues eastward for 4.4 miles (7.1 km) before crossing the Tchefuncte River into Washington Parish.

The highway enters town on Sunset Drive then zigzags south onto Rio Grande Street and east onto Superior Avenue.

Roughly half of the route is classified by the Louisiana Department of Transportation and Development (La DOTD) as a rural minor arterial.

The original highway followed the present LA 1156 through Elizabeth and then travelled along section line roads south and east into Oakdale.

The only major change has been the bypassing of New Roads and St. Francisville resulting from the construction of a cable-stayed bridge across the Mississippi River that replaced the toll ferry connecting the two communities.

[14][43] The John James Audubon Bridge across the Mississippi River was constructed between May 2006 and February 2012 at a location 3.6 miles (5.8 km) downriver from the toll ferry service.

In May 2011, the bridge was opened to traffic early when high water during the 2011 Mississippi River floods caused ferry operations to be suspended.

[53][54] Finally, the present bridge over the Pearl River at the Mississippi state line was constructed in 1998, replacing the original span that existed just to the north.

[12] On December 31, 2010, the Melville Ferry service across the Atchafalaya River between St. Landry and Pointe Coupee Parishes was discontinued, effectively cutting the route of LA 10 in half.

[56] The ferry service and adjoining portions of LA 10 were once part of the main highway route between Baton Rouge and Alexandria and, on a larger scale, New Orleans and Shreveport.

[56] La DOTD is currently engaged in a program that aims to transfer about 5,000 miles (8,000 km) of state-owned roadways to local governments over the next several years.

[60] Under this plan of "right-sizing" the state highway system, two short sections of LA 10 are proposed for deletion as they do not meet a significant interurban travel function.

The remaining portion of LA 10 to be deleted consists of the roadway sections that served the defunct Melville Ferry in Pointe Coupee Parish.

[13][31] It became part of the original route of LA 10 with the 1955 Louisiana Highway renumbering[42][64] and remained so until the Audubon Bridge and adjacent New Roads bypass were opened in 2011.

The western portion, extending from LA 43 (Sitman Street) to the current point of state maintenance, was returned to local control in 2015 as part of the LaDOTD's Road Transfer Program with the remainder proposed for deletion in the future.