The state highway leaves the downtown area and crosses the Appomattox River into Cumberland County.

[1][4] SR 45 heads northeast from the town as Cumberland Road, which passes through the small communities of Raines Tavern, Hawk, Guinea Mills, and McRae on its way to a junction with US 60 (James Anderson Highway).

In Hamilton, the state highway veers east, then turns north next to the historic home Morven to head into Cartersville.

SR 45 bypasses the Cartersville Historic District to the east as it descends to the James River.

The state highway crosses the river immediately upstream of the ruins of the historic Cartersville Bridge.