Concurrencies of US 278 with US highways in Georgia include two long ones with its parent route US 78 from Lithia Springs to Druid Hills, and again from east of Thomson to the South Carolina state line.

Others include US 19/US 41 in the vicinity of Georgia Tech in Atlanta, US 29 from Georgia Tech to Druid Hills, US 23 from the eastern part of Atlanta to Druid Hills, US 129/US 441 in the vicinity of Madison, US 1 from Augusta to the South Carolina state line, and US 25 from Augusta to the South Carolina state line.

The highway starts at the Alabama state line, near Esom Hill in Polk County, and is concurrent with SR 6 from its western terminus.

Along the way, it travels straight east along the north edge of a waterway known as Esom Slough, then turns to the northeast again at the intersection with Brewster Field Road.

This segment of the highway shifts between southeast and east trajectories and, at one point, crosses an at-grade former Central of Georgia Railway line.

The Silver Comet Trail, which travels in close proximity with US 278 from the Alabama state line flanks the highway directly along the south side for the second time east of the bridge over Fish Creek.

The concurrency travels over a bridge above the Silver Comet Trail again, just before the intersection with Atlanta Highway and Coots Lake Road, the former of which was once a segment of US 278/SR 6/SR 101/SR 113.

SR 101/SR 113 leaves the concurrency a little further southeast, and after descending into a slight valley, US 278/SR 6 crosses the Polk–Paulding county line, where the street name is changed to Rockmart Highway.

After the west end of Olivet Loop (another former segment) and at a break in the median, the route officially enters Dallas.

At the intersection of the east end of Olivet Loop and Vista Lake Drive, Rockmart Highway becomes the Jimmy Campbell Parkway.

Curving back to the southeast after the intersection with Hill Road Southwest, the highway travels through a western portion of Austell, where it passes by a major Norfolk Southern Railway yard.

Within "downtown" Austell, US 78/US 278/SR 5/SR 8 becomes Veterans Memorial Highway, makes a sharp right turn and runs along the south side of a railroad line.

East of a bridge over Sweetwater Creek, SR 5 splits from US 78/US 278/SR 8 at an interchange with Markham Road and heads slightly northeast through the western parts of Smyrna to just west of Dobbins Air Reserve Base.

Veterans Memorial Highway ends at the bridge over the Chattahoochee River and becomes Donald Lee Hollowell Parkway Northwest as it enters Atlanta.

After an entrance to that station, the road becomes a divided highway as it travels along the northern edge of Maddox Park, then passes under another railroad bridge containing pylons for a second track.

Almost instantly the divider ends before the intersection with Marietta Boulevard Northwest, then climbs an embankment to a bridge over an abandoned railroad line.

Tunneling under some railroad lines, including some abandoned ones, US 29/US 78/US 278/SR 8 travels between Georgia Tech territory and Coca-Cola owned property.

The southeast corner of Piedmont and Ponce de Leon includes the Savannah College of Art and Design's Ivy Hall Writing Center.

The five highways pass the Briarcliff Plaza shopping center and intersect North Highland Avenue then travels along the southern edge of Atkins Park, where it encounters an intersection with US 23/SR 42 (Briarcliff Road Northeast / Moreland Avenue Northeast), and US 23 joins the concurrency as all four US routes and two state routes cross the DeKalb County line.

On the opposite side, a North Ponce de Leon Avenue runs along the northern edge of Deepdene Park while US 23/US 29/US 78/SR 8 branches off to the northeast traveling along the south side of that park, awaiting the reunification of North Ponce de Leon Avenue with its parent street.

US 278/SR 10 branches off to the southeast onto East Lake Road Northeast, and the first notable feature is the St. Elias Antiochian Orthodox Church, across from a triangle with US 23/US 29/US 78/SR 8, which also has a Jefferson Davis Highway marker.

The intersection with Wire Road seems unimportant other than serving as a de facto connecting route with SR 17, which it will encounter in downtown Thomson.

The concurrency curves to the northeast and then back to the east-southeast, before they cross over Boggy Gut Creek and enter Columbia County.

Just to the southeast of West Boundary Street, they travel about two and a half blocks south of Harlem Middle School.

At the southeastern edge of the city limits, the roadway becomes known as Gordon Highway, which is a major urban corridor farther to the east.

A few thousand feet later, they curve to the northeast, crossing into Richmond County (and the city limits of Augusta), and begin paralleling the northern edge of Fort Eisenhower.

About halfway between here and the interchange with I-520 (Bobby Jones Expressway), the three highways leave the edge of Fort Eisenhower and begin to transition into an urban corridor.

After the interstate, the roadway enters the main part of Augusta, passing south of Aquinas High School, and curves to the south-southeast, past the location of the now-closed Regency Mall.

Two segments had a "completed hard surface": from the Cobb–Fulton county line to Avondale and a portion in the west-southwest part of Augusta.

[40][41] Between June 1963 and the beginning of 1966, SR 21 was extended west-northwest on US 25 Bus./SR 28 (Broad Street) and followed the business route to the South Carolina state line.