Route 100 begins in Burlington as Maple Avenue, at the intersection of NC 54 and NC 49, just north of Interstate 85/40. The route travels north along Maple Avenue through Burlington to its intersection with NC 87. It converges with NC 87, Webb Avenue, into Burlington. After passing under the railroad bridge, NC 87/100 turns west and enters the town of Elon.
Just after crossing into Elon, NC 87 departs and heads to the north and route 100 heads west. Prior to the completion of the Elon Bypass, route 100 used to follow Haggard Avenue into the centre of Elon and through Elon University. However, recent completion of the bypass moved NC 100 north of Elon, and along the bypass, officially known as University Drive. The road passes by the northern edge of the university and Rhodes Stadium, the football stadium. On the west side of Elon, route 100 meets up with Haggard Avenue again and turns into Burlington Avenue.
Route 100 heads west across the Alamance/Guilford county line into Gibsonville. The road makes some turns through Gibsonville, merges with NC 61 and becomes Whitsett Street. After leaving the town, NC 100 and NC 61 head south toward Whitsett. Just prior to entering Whitsett, NC 61 departs. NC 100 finishes its run at U.S. Route 70 in Whitsett.