SR 16 starts just south of Interstate 20 (I-20) in southwestern Haralson County, and travels southeast into Carroll County and Carrollton, where it begins a concurrency with US 27 Alt./SR 1.
SR 16 continues through Whitesburg and crosses into Coweta County and through Newnan, where its concurrency with US 27 Alt.
ends, crossing I-85 on the southeastern edge of East Newnan.

Turning sharply east, the highway travels through Sharpsburg, turns slightly southeast, and travels through Senoia into Spalding County, turning back east, and traveling into Griffin.
Turning slightly northeast, SR 16 crosses I-75 at the county line with Butts County and travels into and through Jackson on into Monticello in Jasper County.

Continuing east, the route crosses into Putnam County, through Eatonton, then turns southeast at the county line with Hancock County, heading on into Sparta.
Turning first slightly northeast, then southeast, SR 16 continues into Warren County, where it turns northeast once more and on to its eastern terminus in Warrenton.

There are four portions of SR 16 that 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:
Approximately 5 miles (8.0 km) in Carrollton, most of it concurrent with US 27/SR 1 and SR 166
The entire length of the concurrency with US 29/SR 14, from Newnan to south of East Newnan.

From US 19/US 41/SR 3 in Griffin east to I-75, approximately 7 miles (11 km) south-southeast of Locust Grove
The portion concurrent with SR 15 in Sparta
SR 16 starts just south of Interstate 20 (I-20) in southwestern Haralson County, and travels southeast into Carroll County and Carrollton, where it begins a concurrency with US 27 Alt./SR 1. SR 16 continues through Whitesburg and crosses into Coweta County and through Newnan, where its concurrency with US 27 Alt. ends, crossing I-85 on the southeastern edge of East Newnan.
Turning sharply east, the highway travels through Sharpsburg, turns slightly southeast, and travels through Senoia into Spalding County, turning back east, and traveling into Griffin. Turning slightly northeast, SR 16 crosses I-75 at the county line with Butts County and travels into and through Jackson on into Monticello in Jasper County.
Continuing east, the route crosses into Putnam County, through Eatonton, then turns southeast at the county line with Hancock County, heading on into Sparta. Turning first slightly northeast, then southeast, SR 16 continues into Warren County, where it turns northeast once more and on to its eastern terminus in Warrenton.
There are four portions of SR 16 that 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:
Approximately 5 miles (8.0 km) in Carrollton, most of it concurrent with US 27/SR 1 and SR 166
The entire length of the concurrency with US 29/SR 14, from Newnan to south of East Newnan.
From US 19/US 41/SR 3 in Griffin east to I-75, approximately 7 miles (11 km) south-southeast of Locust Grove
The portion concurrent with SR 15 in Sparta
Georgia State Route 16