U.S. Route 45W (US 45W) is a 62.33-mile-long (100.31 km) United States Numbered Highway in West Tennessee, connecting Jackson with South Fulton via Humboldt, Trenton, Rutherford, and Union City.

US 45W and SR 5 then rejoin at an intersection with US 70A Bypass/US 79 Bypass, and they leave Humboldt head north through farmland.

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.

US 45W/SR 431/SR 184 goes east through a business district as a 4-lane undivided highway before entering neighborhoods before US 45W/SR 184 split off from SR 431 and follow S Miles Avenue.

2 miles (3.2 km) northeast of Union City, US 51/US 45W has a semi-directional T interchange with the SR 690 (Future I-69) freeway.