SR 5 begins in McNairy County as the hidden designation for US 45 at the Mississippi state line just north of Corinth.

They bypass downtown along the western side as a divided highway before coming to an interchange US 64 Business at the northern edge of town, where US 64/SR 15 split off and US 45/SR 5 leave Selmer and continue north.

US 45/SR 5 then has another intersection with SR 365 before leaving Henderson and continuing northwest to cross into Madison County.

US 45/SR 5 becomes N Highland Avenue as it passes through downtown before entering residential areas and coming to an intersection with US 412 Business/SR 20 (North Parkway) at Old Hickory Mall.

They go northwest as an undivided 4-lane known as E Main Street to pass through residential areas before narrowing to 2-lanes and becomes concurrent with US 70A/US 79/SR 76 (Eastend Drive).

They enter downtown together before splitting there, with US 70A/US 79/SR 76 continuing on W Main Street while US 45W Business/SR 5 go north along N Central Avenue.

US 45W/SR 5 continue north to pass through Rutherford, where it bypasses the town on its west side, and has an interchange with SR 105.

The signed portion of SR 5 exists entirely within Obion County and is approximately 7.8 miles (12.6 km) in length.

TDOT has proposed widening SR 5 in Obion County as part of The 2008-2010 Transportation Improvement Program.

This will leave a two-lane section of SR 5 from Rutherford, Tennessee to a point just north of the Obion River.