The majority of the New Orleans-Baton Rouge section was built parallel to the Louisiana Railway and Navigation Company, which was itself built later than the slightly longer Yazoo and Mississippi Valley Railroad. The former Louisiana Railway, now part of the Kansas City Southern Railway, crosses the Huey Long Bridge with the highway and splits to the northwest towards Shreveport; the extension to Opelousas parallels the New Orleans, Texas and Mexico Railway (later part of the Missouri Pacific Railroad).
