The route makes a wide arc through the Florida Parishes region of the state, traveling east of Baton Rouge and avoiding the urban centers of Hammond and Covington.

However, it passes through a number of the area's smaller towns and communities, such as Denham Springs, Montpelier, Amite City, and Franklinton.

Shortly after crossing into Tangipahoa Parish, LA 16 enters Amite City and passes through an interchange with I-55 at exit 46, connecting with Hammond and Jackson, Mississippi.

LA 16 proceeds through the downtown area and crosses both US 51 (Central Avenue) and the Canadian National Railway (CN) tracks at grade.

[2][4][5][6] After crossing the Tchefuncte River into Washington Parish, LA 16 curves to the northeast and makes a loop through the city of Franklinton.

Near the end of its route, LA 16 enters the northeast corner of St. Tammany Parish and curves due east into the village of Sun.

[citation needed] 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.