The route starts at the Florida state line on a bridge over the St. Marys River in eastern Charlton County, and initially travels north as a four-lane highway through Folkston, concurrent with US 1, US 23, and SR 4/SR 15.

In Hickox, the road curves back towards the north as it briefly widens to accommodate left turn lanes for Brantley CR 79.

Continuing north, crosses a railroad track, and passes by the Hotel Knox, at Broome Street and Florida Avenue, a five-way intersection.

An extra southbound lane forms and then comes to an end just before an intersection with an unnamed dirt road traveling northwest and southeast.

Just before entering Jesup the routes pass by the Jesup-Wayne County Airport, and then the Pine Forest Country Club.

Just before leaving the county, they intersect the southwest terminus of former SR 261, today known as Marcus Nobles Road.

In Glennville, the concurrency makes its strongest effort to move from northwest to northeast at the intersection of SR 196.

After passing a bridge over Chapel Creek, the concurrency travels along the west side of Smith State Prison, where it begins to curve to the north.

The concurrency passes to the east of Union Cemetery and then to the west of Evans Heights Golf Club.

In downtown, the roads pass by The Georgia Fruitcake Company then cross a railroad line right before the intersection with US 280/SR 30/SR 129 (Main Street).

Just northeast of the city limits, US 25/US 301/SR 73 passes southeast of the Claxton Sewage Treatment Pond and the accompanying dam.

Because after the intersection with Bulloch CR 190 the road approaches the real reason for the widening, which is the interchange with I-16 (Exit 116), also known as the Jim Gillis Historic Savannah Parkway.

North of SR 46 the divider comes to an end, but US 25/US 301/SR 73 remains a four-lane highway with provisions for left turn lanes.

North of the bypass, the routes travel along South Main Street which passes just to the west of Georgia Southern University and later cuts between the W. Jones Lane Memorial Park and Charles H. Henry Pines Nature preserve.

[7] The rest of the area contains random local commercially zoned properties until it reaches the Bulloch County Sheriff's Office and Correctional Facility, and then the northeast terminus of US 301 Bypass/SR 73 Bypass, where the road officially leaves the city.

The road descends slightly along the landscape between some local businesses before crossing a bridge over Mill Creek, then curves towards the north, where it approaches offices for the Bulloch County Animal Shelter, a local Georgia Forestry Commission facility, and the Statesboro–Bulloch County Airport.

North from there the route enters Clito, where it travels past an independent motel called the Mill Creek Lodge, and then passes the intersection of Kyle Sorrell Road, which has the Statesboro Mission Outreach Ministries[8] on the southwest corner, and a gas station and convenience store on the northwest corner.

A power line right-of-way crosses US 301/SR 73 from southwest to northeast, and then travels parallel to the routes across the street from the Oak Hill manufactured home development.

Beyond that point, the power lines are obstructed by trees, and the routes descend as they approach a culvert over Lily Creek.

The road immediately enters Dover with the name Statesboro Highway and after the first intersection within the county, crosses a bridge over a railroad line.

Shortly it travels under a power line right-of-way, and then approaches a blinker-light intersection with the first major crossroad in Screven County; SR 17, although some maps indicate that this is actually in Cooperville.

Various run-down local businesses can be found on both sides before the route enters the Sylvania City Line Right after the intersection of Waters Station Road, US 301/SR 73 becomes a divided highway flanked by a frontage road on the southbound side, before approaching the intersection of and south end of the concurrency with SR 21.

The division ends in front of the Village Green Motel just before leaving the city limits, and curves to the northeast with the name Burton's Ferry Highway.

North of there, the surroundings include more forest land than farmland, even as it curves to the northeast before crossing a bridge over the swamps of Brier Creek.

After the intersection with Oglethorpe Trail and Old River Road, US 301/SR 73 curves to the east before encountering Georgia's first Welcome Center,[9] which has been listed on the National Register of Historic Places since December 29, 2011.

The existing US 301/SR 73 travels around the former section as it approaches the 1965-built Burton's Ferry Bridge[10] which is parallel to the former Parker Truss Swing Bridge from 1938[11] both of which cross over the Savannah River and the state line with South Carolina, where SR 73 officially terminates, while US 301 continues through the Carolinas, Virginia, Maryland, and Delaware.

[25][26] In July, the entire Tattnall County portion of the segment of SR 23 from Ludowici to south of Glennville also had a completed hard surface.

[31][32] In the first half of 1936, the southern part of the segment of SR 73 from north of Sylvania to the South Carolina state line had completed grading, but was not surfaced.

Nearly the entire Evans County portion of the segment of SR 73 from Claxton to southwest of Statesboro was under construction.

[44][45] By the middle of 1941, the segment of US 25/SR 73 from the Evans–Bulloch county line to SR 46 southwest of Statesboro also had a completed hard surface.