Its southern terminus is at the Florida state line south-southeast of Thomasville, where the roadway continues as US 19/SR 57.

Most of the route of SR 300 in Albany is on the Liberty Expressway, a freeway-grade bypass of the city's downtown to the northeast.

They join the US 19/SR 3/SR 133 concurrency, while US 82/SR 300/SR 520 head east for just over 1.5 miles (2.4 km), where SR 300 splits off to the northeast.

Upon entering Cordele, the route meets its northern terminus, an interchange with I-75.

[7][8] By October 1929, SR 3 was extended southwest to where US 319 currently crosses the state line.

SR 35 was designated along a portion of highway that is the current route of US 19 from the Florida state line to Thomasville.

[8][9] By 1935, nearly all of the northern half of the section of SR 35 between the Florida state line and Thomasville was paved.

[21][22] In early 1946, approximately half of the length of SR 133 between Warwick and Cordele was paved.

[27][28] A section of the highway from Albany to Cordele was proposed as Interstate 175 and then cancelled, but in early 1982, the Georgia–Florida Parkway was approved to be designated along the entire stretch of what is now SR 300.