MS 12 begins the
Mississippi Delta region in
Washington County at an intersection with
MS 1 (part of the
Great River Road) thirteen miles south of
Greenville, not even a mile from the banks of the
Mississippi River, and only five miles north of
Lake Washington. The highway heads east through flat farmland as a two-lane highway to travel through
Leroy Percy State Park, where it crosses
Silver Creek Bayou, before entering
Hollandale. MS 12 enters town along W Washington Street, makes a right in downtown onto East Avenue S, then left onto E Crouch Street to cross
Deer Creek and come to an intersection with
US 61. The highway now leaves Hollandale and continues east through rural farmland for several miles to cross the
Sunflower River into
Humphreys County. MS 12 continues east through farmland for several miles to enter
Belzoni and immediately come to an intersection between
US 49W (unsigned
MS 3) and
MS 7 just west of downtown. The road continues as MS 7 (1st Street) into downtown while MS 12 becomes
concurrent with US 49W/MS 3 and they head south as a four-lane to bypass downtown. MS 12 breaks off as a two-lane shortly thereafter and goes east to cross the
Yazoo River to leave Belzoni. The highway continues east through rural farmland and woodlands for several miles to enter
Holmes County. MS 12 crosses
Tchula Lake before traveling along the southern edge of
Marcella and coming to an intersection and becoming concurrent with
US 49E. They head northeast for a few miles to travel through
Mileston before entering
Tchula, with MS 12 splitting off and heading east just south of downtown. MS 12 climbs some
Loess bluffs onto the North Central Hills region, crossing
Fannegusha Creek and passing in between the
Morgan Brake National Wildlife Refuge and the
Hillside National Wildlife Refuge. It now travels southeast through woodlands for several miles to enter
Lexington. The highway passes through neighborhoods before turning south and becoming concurrent with
MS 17 at a Y-Intersection. MS 12/MS 17 continue along Carrollton Street through neighborhoods to enter downtown, with MS 12 splitting off along Depot Street at a
Roundabout around the Holmes County Courthouse. The highway heads east to leave downtown to cross a creek and have an intersection with
MS 836 (the new Lexington Bypass) before heading through a business district. It crosses another creek before leaving Lexington and traveling through some farmland and wooded areas for several miles, where it passes through
Owen Wells, to have an interchange with
I-55 (Exit 156) and entering
Durant. MS 12 heads southeast through a business district before turning south along
US 51 (N Jackson Street) through neighborhoods into downtown. MS 12 splits off along E Mulberry Street at the center of town, heading east to cross some rail road tracks to pass through more neighborhoods before leaving Durant and traveling through swamplands, crossing the
Big Black River into
Attala County. MS 12 travels through a mix of farmland and wooded areas for the next several miles, passing through
Sallis, where it has intersections with
MS 429 and
MS 431, and
McAdams, before becoming concurrent with
MS 43 and entering
Kosciusko. The highway bypasses downtown along its western and northern sides, having intersections with
MS 735, splitting off from MS 43, as well as having intersections with
MS 19 and
MS 35. MS 12 now leaves Kosciusko and heads northeast through woodlands to have an interchange with the
Natchez Trace Parkway before traveling through
Ethel, bypassing the town to the north while its business loop,
MS 739, passes straight through downtown. The continues northeast through wooded areas for several miles to pass just west of
McCool, where it has its first intersection with
MS 407 (as well as with
MS 411), before crossing into
Choctaw County. Between Kosciusko and Ackerman, MS 12 runs parallel to the
Yockanookany River. MS 12 continues northeast through woodlands to travel through
Weir, passing along the north side of town to have intersections with
MS 413 and its second and final with MS 407, before entering
Ackerman. The highway passes along the northern side of town, bypassing downtown as it travels through a business district and has intersections with
MS 9,
MS 15, as well as with its unsigned business loop
MS 759 (W Main Street/College Street). MS 12 now leaves Ackerman and winds its way east through remote, hilly, and wooded terrain for the next several miles to cross into
Oktibbeha County. This section of the highway lies within the
Tombigbee National Forest. MS 12 now enters the
Golden Triangle region and travels through
Sturgis,
Bradley, and
Longview before entering
Starkville to have an interchange with
MS 25 in some neighborhoods. The highway widens to a four-lane undivided boulevard as it passes along the north side of
George M. Bryan Airport and passes through a major business district on the south side of downtown. MS 12 makes a sharp curve to the north at an interchange with Bully Boulevard (unsigned
MS 775), the main access into
Mississippi State University. The highway now becomes a four-lane divided expressway, having interchanges with Collegeview Street and
MS 182, before joining the
US 82/MS 25 four-lane freeway. US 82/MS 12/MS 25 head east to leave Starkville and pass through
Clayton Village, where it has another intersection with MS 182, before heading through farmland to cross into
Lowndes County. The freeway immediately has an interchange with
US 45 Alternate, where MS 25 splits off, and US 82/MS 12 continues east to pass through
Mayhew, and have an interchange with
MS 791 (which provides access to
Golden Triangle Regional Airport), prior to entering
Columbus. The freeway has an interchange and becomes concurrent with
US 45 before crossing a bridge over the
Tombigbee River (part of the
Tennessee Tombigbee Waterway) and bypassing downtown to the north, having interchanges with MS 182,
MS 69 (where US 45 splits off and
MS 50 joins the concurrency), as well as 18th Avenue N and Military Road, before crossing over
Luxapalila Creek. MS 12/MS 50 split off the US 82 freeway at an interchange with Tuscaloosa Road, with them heading east through a business district as a four-lane boulevard, with MS 12 splitting off and heading north as a two-lane shortly thereafter. MS 12 leaves Columbus and travels northeast through farmland for the next several miles, where it crosses another bridge over Luxapalila Creek and passes through
Woodlawn (as well as having intersections with Seed Tick Road and Caledonia-Vernon Road, both of which are county roads that lead to nearby
Caledonia), before coming to the
Alabama state line, with the road continuing east into Alabama as
State Route 18 (SR 18). ==Major intersections==