SR 216 begins at an intersection with SR 37 northwest of Newton, in central Baker County. It heads northwest, crossing into Early County, until it reaches Arlington. Almost immediately is an intersection with SR 45 (Joe Bryan Highway), which begins a concurrency with SR 216. Just after this is SR 62 (Blakely Road SW), which joins the concurrency. In downtown Arlington, the three highways enter Calhoun County and cross a Norfolk Southern Railway track. Then, SR 62 departs to the northeast on Pioneer Road. Two blocks later, SR 45 leaves the concurrency to the northeast on Morgan Road NE. SR 216 heads north to Edison, where it has a brief concurrency with SR 37 (Hartford Street). The highway heads north, curves to the northwest, and then curves back to the north, until it enters Randolph County. It continues heading north until it meets is northern terminus, an intersection with US 27/SR 1, just south of Cuthbert.