US 49W begins just north of downtownYazoo City at an interchange between US 49 and US 49E. It heads northwest to have an interchange with and become concurrent with MS 3 before leaving Yazoo City and crossing over the Yazoo River. The highway then crosses into Humphreys County just southwest of Carter. US 49W/MS 3 now cross over the Will M. Whittington Auxiliary Channel and Lake Atchaflya before passing through Silver City and having an intersection with MS 149. The highway continues north, paralleling the Yazoo River, to pass through Belzoni, where it bypasses downtown along its west side and has a short concurrency with MS 12 and an intersection with MS 7. US 49W/MS 3 continue northwest to pass through Isola, where it has an intersection with unsigned MS 806 and crosses over Lake Dawson, before entering Sunflower County. The highway passes through Caile and Inverness, where it intersects another section of MS 149, before MS 3 splits off towards Moorhead near Baird. US 49W crosses over the Sunflower River to enter Indianola. It bypasses downtown along its east side, passing through neighborhoods to have an intersection with US 82. The highway then narrows to two-lanes to leave Indianola and cross the Sunflower River for a second time. Prior to this point, the entire route of US 49W is a four-lane highway. US 49W passes through Sunflower, where it intersects unsigned MS 810 and rejoins MS 3, before passing through Dwyer and Blaine. US 49W/MS 3 passes through Doddsville, where it has a short concurrency with MS 442 and intersects unsigned MS 832, and Cottondale before passing through Ruleville, where it has an intersection with unsigned MS 812 and MS 8. The highway passes through Drew, where it intersects unsigned MS 820, before passing by the Mississippi State Penitentiary, where it has an intersection with MS 32. US 49W/MS 3 pass through Rome before entering Tallahatchie County. The highway passes northeast through rural areas for several miles before entering Tutwiler and coming to an end at a Y-Intersection between US 49 and US 49E, with MS 3 continuing north along US 49.
