The highway travels from the Alabama state line west of Cave Spring northeast, then east, then southeast to US 129 Bus./US 441 Bus./SR 15/SR 24 Bus.

From its western terminus at the Alabama state line, SR 53 travels east through Floyd County, co-signed with US 411.

Just to the east of downtown, SR 53 departs from the other routes and travels northeast, running parallel to the Oostanaula River and through Shannon into Gordon County.

After running northeast into Hall County and crossing the Chestatee River branch of Lake Lanier, the route again turns to the southeast, then crosses over the Chattahoochee River branch of Lake Lanier.

The route continues to head southeast, briefly becoming co-signed with SR 211, then crosses into Jackson County and intersects I-85 in Braselton.

In Floyd County, average traffic loads west of Rome hover around 4,000 vehicles per day, with a maximum of 5,000 in Cave Spring.

South and east of Winder, averages drop down to between 3,500 and 5,000 vehicles per day, but then increase one last time to just under 16,000 in Watkinsville, as the route reaches its eastern terminus.

[2] The following portions of SR 53 are part of the National Highway System, a system of routes determined to be the most important for the nation's economy, mobility, and defense: The first portions of the roadway that is signed as SR 53 today makes its appearance on Georgia state road maps in 1921, which show the portion of the route from south of Calhoun, through Fairmount, and on to Jasper.

Another large portion of the route, running from Jasper to Dawsonville, on to Gainesville, and continuing to Winder, had also been graded by 1929, but did not appear to be signed yet.

About half of the route out of Rome had also been improved to hard surface, and the same was the case for the entire portion between Fairmount and Jasper, as well as more than half of the portion between Jasper and Dawsonville, and part of the stretch between Gainesville and Winder.

In addition, the entire existing route, from Rome to Winder, was signed as SR 53 by 1932.

[9] The final stretch of the main route of SR 53 appeared in August 1933, when the portion from Winder to Watkinsville was shown as graded but unimproved for the first time.

[10] By early in 1935, the only change of note to the route was the fact that the portion from the Alabama state line to Rome had by then been co-signed with US 411.

[12] It was 1953 before the entirety of the route was marked on Georgia highway maps as having been covered with hard surface.

[18] As of 2014, GDOT plans to demolish the steel-truss bridge that carries Georgia 53 over Lake Lanier at the Forsyth/Hall county line.

Built when the Chestatee River was flooded to create the lake, the Boling Bridge will be replaced with a much more bland[citation needed][original research?]

First from the intersection with Mars Hill Road/Hog Mountain Road to its interchange with US 441/US 129/SR 24, all of which is west of Watkinsville (Phase II).