The route runs south as Hervey Street through downtown Hope past the Foster House and the Bill Clinton Birthplace both two properties being National Register of Historic Places (NRHP) listed.

Despite its designation, the route only meets US 278 at its eastern terminus and does not connect back to US 278 west of Monticello.

Its entire length is concurrent with State Route 6 Business (SR 6 Bus.).

It travels to the southeast and immediately crosses over the Silver Comet Trail.

It enters the city limits of Rockmart and passes by Rose Hill Cemetery.

Then, it crosses over Euharlee Creek and the Silver Comet Trail again on the Raymond Lester Bridge.

At Piedmont Avenue, the business route turns to the north, remaining along that street for the rest of its journey.

US 278 Truck/SR 12 Truck begins at mainline US 278/SR 12 and SR 83, which turns northeast at a fork in the road as those routes head into historic downtown Madison.

At this intersection, SR 24 Spur (Ward Road), which also begins here, has a concurrency with US 278 Truck/SR 12 Truck.

The highways travel to the south until they reach an intersection with the southern terminus of US 129 Byp./US 441 Byp./US 441 Truck/SR 24 Byp./SR 24 Truck.

The only portion of US 278 Truck and SR 12 Truck that is part of the National Highway System, a system of routes determined to be the most important for the nation's economy, mobility, and defense, is the portion concurrent with US 129/US 441/SR 24.

is a 1.6-mile-long (2.6 km) bypass route of US 278 that exists entirely within the city limits of Warrenton, Georgia.

begins at mainline US 278/SR 12, which turns from southeast to straight east as those highways head into historic downtown Warrenton.

The road serves as the northern terminus of SR 171 across from the Warren School Bus Shop, and then begins to curve to the northeast, even more so when it approaches SR 80 (Quaker Road) which joins the bypass in a concurrency.

ends at a second intersection with US 278/SR 12, and SR 80 continues north towards Waynesboro and Shell Bluff.

is a 8.990-mile (14.468 km) business route of US 278 that is entirely within the city limits of Hilton Head Island.