DE 100 begins at an intersection with DE 4 southwest of the city of Wilmington, heading north on the one-way pair of Race Street northbound and South Dupont Road southbound. The one-way pair, which carries two lanes in each direction, passes through suburban residential areas. Both directions of the route join, with the route continuing northwest as South Dupont Road, a four-lane divided highway. DE 100 curves north and enters the town of Elsmere, where it runs through industrial areas and comes to a bridge over Little Mill Creek, B&O Lane, CSX's Philadelphia Subdivision railroad line, and Baltimore Avenue. A short distance later, the route crosses DE 2 and the name changes to North Dupont Road, where it becomes an undivided road and passes over an East Penn Railroad line on a bridge. The road continues through wooded residential areas, leaving Elsmere and becoming South Dupont Road. The route reaches an intersection with the eastern terminus of Faulkland Road. Following this intersection, DE 100 passes to the east of a cemetery before reaching an intersection with DE 48 south of the Cab Calloway School of the Arts and Charter School of Wilmington.