LA 16 proceeds through the downtown area and crosses both US 51 (Central Avenue) and the Canadian National Railway (CN) tracks at grade. East of Amite City, LA 16 crosses the Tangipahoa River and proceeds toward Washington Parish via Holton. After crossing the Tchefuncte River into Washington Parish, LA 16 curves to the northeast and makes a loop through the city of Franklinton. This portion of the route overlaps both LA 10 and LA 25 and contains a bridge spanning the Bogue Chitto River that leads onto Washington Street, the city's main east–west thoroughfare. LA 16 turns south from Washington Street onto Main Street and separates from LA 10 and LA 25. South of town, LA 16 parallels the Bogue Chitto River and travels southeastward through Enon, where it intersects LA 60. 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. Here, it reaches its eastern terminus at a junction with LA 21, connecting with Bush to the south and Bogalusa to the north. In the original Louisiana Highway system in use between 1921 and 1955, LA 16 was part of several different routes, including State Route 331 from the western terminus to Port Vincent; State Route 131 to Denham Springs; State Route 337 to Watson; State Route 103 to Amite City; State Route 35 to Franklinton; and State Route 469 to Sun. These highways were joined together under the single designation of LA 16 when the Louisiana Department of Highways renumbered the state highway system in 1955. Despite its length, the alignment of LA 16 has remained virtually the same since the 1955 renumbering. Alterations to the route have been limited to the smoothing of some curves, the replacement of bridges, and the addition of lanes in urban areas. In 2008, an approximately stretch of LA 16 in the Denham Springs and Watson areas was widened from two to four lanes. This was in response to the large amount of daily traffic the area experienced in the past decade. (Watson was at one time in the early 2000s the largest growing area in the state of Louisiana). La DOTD is currently engaged in a program that aims to transfer about of state-owned roadways to local governments over the next several years. Under this plan of "right-sizing" the state highway system, the portion of LA 16 that follows Pete's Highway on the south side of Denham Springs is proposed for deletion in favor of the parallel LA 3002 as it no longer meets a significant interurban travel function.