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. After , the route intersects LA 1048, which leads to another interchange with I-55. Just south of this intersection, at a point known as Arcola, LA 10 resumes its eastward course and separates from US 51, which continues south through Roseland and Amite City toward Hammond. After crossing a bridge over the Tangipahoa River, LA 10 begins to travel in a general northeastern direction and intersects the rural highways LA 1058, LA 1054, and LA 1061 over the next . The latter junction is located in an area known as Wilmer, and LA 10 continues eastward for before crossing the Tchefuncte River into Washington Parish.