SR 59 begins at an intersection with U.S. Route 441 (US 441)/SR 15 (Homer Road) in the northeastern part of Commerce within Jackson County. This intersection also marks the northern terminus of US 441 Business/SR 15 Alternate, which take the Homer Road designation. South of here, US 441/SR 15 are known as Veterans Memorial Parkway. Almost immediately, SR 59 crosses into Banks County. The only major intersections in the county are with the eastern terminus of SR 164 and the southern terminus of SR 63. In Franklin County, it intersects SR 51 before meeting the eastern terminus of SR 198. Less than 1 mile (1.6 km) later, the highway intersects SR 106, which travels concurrent with it into Carnesville. In town, SR 145 joins the concurrency for just over 1 mile (1.6 km). At the end of the concurrency, SR 59 splits off to continue its northeast routing. In Lavonia, SR 59 intersects SR 17, before meeting the northern terminus of SR 77 Connector. About two miles (3.2 km) later, the road crosses into Hart County. It intersects SR 77 and the state highway ends. The road continues to the northeast and curves to the east before ending along the northwestern shore of Lake Hartwell.
Before the construction of Lake Hartwell, SR 59 continued into South Carolina as South Carolina Highway 59. With the I-85 bridge less than 1 mile (1.6 km) away from the old crossing, the states had no need to directly reconnect the roads. SR 59 is not concurrent with I-85 on either side of the lake and the two highways do not officially connect.
The section of SR 59 between SR 77 and the shoreline of Lake Hartwell was transferred to county maintenance between 1990 and 1993.