They bypass downtown along the western side as a divided highway before coming to an interchange US 64 Bus.

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 Bus./SR 20 (North Parkway) at Old Hickory Mall.

US 45/SR 5 passes through a business district before a single point urban interchange (SPUI) with I-40/US 412 (exit 82).

[4] Mainline US 45, concurrent with unsigned SR 3, goes northeast and passes through neighborhoods in South Fulton along Chickasaw Drive before turning north onto Highland Drive at an intersection with Kentucky Route 116 (KY 116, W State Line Street) at the western edge of downtown.