Excluding the route through West Point, the entire length of US 45 Alternate is a four-lane divided expressway, with interchanges at most major junctions.

US 45 Alternate enters the Golden Triangle region as it bypasses Crawford along its east side, with MS 245 passing through the center of town, before traveling through Penns and Artesia.

The highway becomes an undivided four-lane boulevard and passes north through a business district and neighborhoods, where it has an intersection with MS 50 (Main Street) on the west side of downtown.

US 45 Alternate now re-enters Monroe County as it bypasses Okolona on its east side, where it has an interchange with MS 41.

US 45 Alternate crosses Chiwapa Creek to enter the Shannon city limits, with the highway coming to an end shortly thereafter at an interchange between US 45, US 278, and MS 145, with the four-lane continuing north into Tupelo (and on to I-22) as US 45.

were upgraded to a four-lane highway,[14] and Crawford was bypassed as a result, with MS 245 being designated along the old route through town.