Shelby County

SR 57 starts in Memphis by going south on Trezevant Street from SR 14 (Jackson Avenue). Trezevant St. turns into East Parkway (at an intersection with SR 1) and follows US 70/US 79/US 64 and SR 277. They have an intersection with Sam Cooper Boulevard before SR 57 turns east and follows US 72 along Poplar Avenue, where it starts to follow the Norfolk Southern Railway to the north. Poplar Avenue has an interchange with I-240 in East Memphis and soon enters Germantown, where it is briefly overlapped with SR 177. As the road enters Collierville, it becomes known as West Poplar Avenue (instead of Poplar Avenue). SR 57 meets Byhalia Road (which becomes Mississippi Highway 309 (MS 309) at the Mississippi state line) as a crossroads. Just east of that intersection US 72 diverges from SR 57 by going southeast into Mississippi, via unsigned SR 86, while SR 57 continues east along West Poplar Ave. SR 57 becomes a two-lane road but remains at a 40 mph (64 km/h) speed until it exits Collierville. East of the Collierville town square, it becomes East Poplar Avenue and SR 205 (Collierville-Arlington Road) has its southern terminus at SR 57.

Poplar Avenue is a major thoroughfare through Shelby County and has much commercial development along its route. In the city of Memphis, the road is locally known for its narrow lanes of traffic and hazardous storm grates along its edges. The many freight trains that run along the side of it cause several traffic delays throughout the day.

Fayette County

When SR 57 enters Fayette County, the speed limit increases to 55 mph (89 km/h) and except for when the road passes through a town, it remains at this speed until it ends in Mississippi. Just outside Collierville, SR 57 has an interchange with I-269. In the city of Piperton, SR 57 intersects with SR 196 and crosses over the Norfolk Southern Railway. A few miles down the road, it passes through Rossville and is the southern terminus for SR 194. SR 57 passes over the Wolf River and passes through Moscow. The southern terminus of SR 76 occurs in Moscow. Several miles down the road from here, SR 57 passes through LaGrange. Motorists can view several of the town's historic buildings from the road. East of LaGrange, SR 57 turns left along SR 18, passes over the Norfolk Southern Railway again, and then continues east.

Hardeman County

SR 57 in Pocahontas

After splitting from SR 18, SR 57 enters Hardeman County and also enters Grand Junction. It is home to the National Bird Dog Museum, which is visible from the road. SR 57 crosses over the Mississippi Central Railroad and junctions with SR 368. Several miles east is the town of Saulsbury. East of Saulsbury, SR 57 passes over the Norfolk Southern Railway for a third time, and continues east to Middleton. Here, it intersects with SR 125 and crosses the Mississippi Tennessee Railroad. East of Middleton, SR 57 goes through the town of Pocahontas, where it passes over the Norfolk Southern Railway for the fourth and final time. The railroad continues southeast into Mississippi while SR 57 continues east. It also passes over the Hatchie River around Pocahontas.

McNairy County

SR 57 enters McNairy County and passes north of Big Hill Pond State Park. SR 57 passes through Ramer, where it is the northern terminus of SR 234. It also crosses over the West Tennessee Railroad (also owned by Norfolk Southern Railway). SR 57 continues east and crosses US 45 near the town of Eastview. after crossing US 45, SR 57 goes north of the town of Michie and intersects with SR 224. East of Michie, the road junctions with SR 22, which is the most direct route to Shiloh National Military Park.

Hardin County

SR 57 passes into Hardin County and intersects with SR 142 west of the town of Counce. When SR 57 enters the town of Counce, it crosses a railroad spur of the Kansas City Southern Railway. East of the town, the road intersects with SR 128 in Pickwick Village. SR 128 goes north over Pickwick Dam, and SR 57 turns right and heads south toward Pickwick Landing State Park. SR 57 continues south along Pickwick Lake for approximately 5 miles (8.0 km) until it crosses into Mississippi and becomes Mississippi Highway 25.