U.S. Route 45E (US 45E) is a 61.23-mile-long (98.54 km) state highway in West Tennessee, connecting Jackson with South Fulton via Milan and Martin.

[2] US 45E/SR 43 immediately enters Medina, where the highway bypasses downtown on the western side and has an intersection with SR 152.

It then leaves Medina and continues north to enter Milan and has an intersection with SR 187 before becoming an undivided four-lane highway as it passes through residential areas.

The highway then crosses the South Fork of the Obion River to enter Weakley County.

US 45E then comes to an end at an interchange between US 51, US 45W, US 45, and unsigned SR 3, just feet from the Kentucky state line.

is a 4.0-mile-long (6.4 km) business route of US 45E that travels along that highway’s former alignment through downtown Martin, Tennessee.

It heads north through rural areas as a two-lane highway for a little over a mile before passing through a business district and some neighborhoods.