Southern segment MS 43,
concurrent with
MS 603, begins in
Hancock County just west of
Bay St. Louis in
Waveland at an intersection with
US 90. The highway heads north through a business district as a four-lane undivided boulevard before widening to a divided highway as it leaves Waveland and curves to the northwest. MS 43/MS 603 pass through the suburban community of
Shoreline Park for the next several miles to cross
Bayou La Croix and have an interchange with
I-10 at Exit 13. The heads northward through rural terrain for the next few miles, where it narrows to two-lanes and has an intersection with the access road for
Stennis International Airport, which also houses many of the county's services. MS 43/MS 603 meet Texas Flat Road before crossing the
Jourdan River and passing through the town of
Kiln, where MS 43 splits from MS 603. MS 43 passes northwestward through rural areas (and the community of
Wiehe) for several miles, crossing the Jourdan River for a second time, before entering
Pearl River County. MS 43 heads west through farmland to enter the city of
Picayune, where it passes through neighborhoods before widening to a four-lane divided highway and coming to an interchange with
I-59 (Exit 4), with MS 43 following I-59 north to Exit 6, where it crosses
Hobolochitto Creek. MS 43 heads west from Exit 6 as a four-lane divided highway through a mix of neighborhoods and businesses to have an intersection with
US 11. The highway narrows to two-lanes as it leaves Picayune, crossing Hobolochitto Creek again before having an intersection with MS 43 Spur (
MS 992/Beech Street). MS 43 winds its way northwest through farmland and wooded areas for several miles, passing through the
Cybur community, before turning northward and coming to an intersection with
MS 26 at the
Crossroads community. The highway now parallels the
Pearl River as it winds its way north through wooded areas for several miles to cross into
Marion County, coming to an end shortly thereafter at an intersection with
MS 13 between
Columbia and
Lumberton.
Middle segment MS 43 begins in
Jefferson Davis County at an intersection with
MS 13 just north of
Society Hill and heads west as a two-lane highway through woodlands to pass through
Oak Vale, where it crosses into
Lawrence County. MS 43 turns northwest through farmland, passing through
Arm, before crossing the
Silver Creek and having an intersection with
MS 43A. The highway continues northwest to have a short concurrency with
MS 184, just across the
Pearl River from
Monticello, before joining
US 84 east for a few miles. US 84/MS 43 enter the
Silver Creek city limits at another intersection with MS 184 before MS 43 splits off at an intersection with MS 43A, winding its way through town along Front Street, where it has its final intersection with MS 184 (Southern Avenue). MS 43 leaves Silver Creek and heads northeast to enter
New Hebron, where it passes through town along Jones Street, Main Avenue, and Franklin Street, having intersections with both
MS 915 (unsigned/Jones Street) and
MS 42 (Indiana Avenue). The highway heads north to leave New Hebron and straddle the line with Jefferson Davis County before crossing into
Simpson County. MS 43 heads northeast through a mix of woods and farmland as it has an intersection with
MS 478 and passes through
Shivers. It then comes to an intersection with
MS 28, which it briefly follows westward as it has an intersection with
MS 472 and passes through
Pinola. The highway winds it way northeast as it parallels the
Strong River for several miles before entering
Mendenhall and immediately coming to an end at another intersection with MS 13 just west of downtown.
Northern segment MS 43 begins in
Rankin County in
Puckett at an intersection with
MS 18 just northwest of downtown. It winds its way northward as a two-lane highway through farmland for several miles to have an interchange with
I-20 (Exit 68) before passing through
Pelahatchie, where it has an intersection with
US 80. The highway winds its way northwest to have an intersection with
MS 481 before passing through
Sand Hill,
Koch (where it has an interchange with
MS 25), and
Goshen Springs (where it has an intersection with
MS 471) before crossing a
Causeway over the
Ross Barnett Reservoir (part of the
Pearl River) into
Madison County. MS 43 immediately has an interchange with the
Natchez Trace Parkway at
Madisonville before passing northward through
Canton, bypassing downtown along its eastern side while having a short
concurrency with
MS 16. The highway now turns northeast through mostly wooded areas for the next several miles, where it passes through
Sharon, before crossing into
Leake County. MS 43 begins paralleling the Natchez Trace as it passes through the community of
Thomastown, where it has a junction with
MS 429, before continuing northeast for several more miles before crossing into
Attala County. MS 43 becomes concurrent with
MS 14 for a couple of miles to enter the
Kosciusko outskirts, where it follows a beltway around downtown while having an intersection with
MS 735 and concurrencies with
MS 12,
MS 19, and
MS 35. The highway heads north out of Kosciusko through remote terrain for several miles to the
Montgomery County line, where MS 43 comes to an end at an intersection with Winfry Road. Access to
MS 407 can be achieved via a right onto Winfry Road for a before turning left onto Ellis Road for . ==Major intersections==