The highway connects the southeastern portion of Carroll County, northwest of Mount Zion to Warrenton, via Carrollton, Newnan, Griffin, Monticello, Eatonton, and Sparta.

SR 16 continues through Whitesburg and crosses into Coweta County and through Newnan, where its concurrency with US 27 Alt.

There are four portions of SR 16 that are part of the National Highway System, a system of routes determined to be the most important for the nation's economy, mobility, and defense: SR 16 was established at least as early as 1919 on its current path from Carrollton to Warrenton.

[2]/[5] By October 1926, this extension was redesignated as part of a southern segment of SR 8.

Two segments of SR 16 had a "completed hard surface": a portion in the southern part of Newnan and from Griffin to just east of the Henry–Butts county line.

[5][6] Between October 1929 and June 1930, a portion of SR 16 west-southwest of Griffin was completed.

[10][11] At the end of the next year, the Jasper County portion of the Jackson–Monticello segment was completed.

[14][15] About a year later, a small portion in the eastern part of Monticello was completed.

[27][28] Between February 1948 and April 1949, the Putnam County portion of the Eatonton–Sparta segment was hard surfaced.

The former part from northwest of Wrens to north of Louisville was redesignated as SR 16 Conn.[32][33] Between June 1955 and July 1957, the Warrenton–Wrens segment was paved.

[40][41] Later in 1980, the path of US 27 Alt./SR 16/SR 166 in Carrollton was shifted southward, out of the main part of the city, onto the previously proposed bypass.

SR 16 then traveled north on a concurrency with US 27/SR 1 to its original intersection with those two highways.

[34][35] In 1973, the path of SR 16 in the city was shifted southward, replacing all of the spur route, except for the western part.