SR 45 begins at an intersection with US 84/SR 38 (Dunham Street) in Iron City, in Seminole County.

It enters Colquitt, passing Pleasant Hill Cemetery and curving to the northwest.

The four highways head east, crossing over Spring Creek into the main part of town.

SR 45 heads nearly due north and gradually curves to the north-northeast before entering Early County.

It passes through rural areas of the county and enters Morgan, where it has a very brief concurrency with SR 37.

The highway heads north, curves to the northeast, and then to the east, crossing over Ichawaynochaway Creek.

In town, they pass Dawson Country Club and cross over Brantley Creek, before intersecting SR 520.

Its route travels totally within the city limits of Colquitt and is known as South First Street for its entire length.

It curves to a nearly-due-north routing for one block and meets its northern terminus, an intersection with SR 45/SR 91 in the main part of town.

The concurrency curves again to the southeast and intersect the southern terminus of SR 91 Spur, where the truck routes leave US 27/SR 1.

The two highway travel to the west for five blocks, to an intersection with SR 45, which is on the northeast corner of the Miller County Courthouse.

is a 0.4-mile-long (0.64 km) alternate route that exists entirely within the southwestern part of Calhoun County.

Its route is also completely within the city limits of Arlington and is concurrent with SR 45 Truck for its entire length.

It begins at an intersection with SR 45/SR 62/SR 216 (Highland Avenue North), in the central part of Arlington.

Then, they turn left onto Mayhaw Avenue NE and travel north-northwest through town.