DE 15 serves several cities and towns, including Wyoming, Dover, Clayton, and Middletown.

DE 15 has a junction with Carpenter Bridge Road before it heads across the Murderkill River to the east of Coursey Pond.

The route intersects DE 12 and heads across Pratt Branch before it runs to the east of Henderson Aviation Airport.

[3][4] DE 15 turns north to form a concurrency with US 13 for a short distance on the four-lane divided South Dupont Highway before continuing northwest along with US 13 Alt.

DE 15 turns east onto Westville Road and enters the town of Wyoming, where it becomes Southern Boulevard and passes homes and some businesses.

At this point, DE 15 becomes Wyoming Mill Road and heads north through agricultural areas away from the railroad tracks.

The road continues through farmland with some woods and residential development before entering the city of Dover and curving to the northwest.

The road continues through more commercial areas and comes to an intersection with DE 8, where it is briefly a divided highway.

The route turns into a divided highway for a short distance at the College Road intersection before becoming undivided.

Past Scarborough Road, the route heads northwest near an industrial park before it leaves Dover.

The road crosses Mill Creek and an abandoned railroad line before it comes to an intersection with DE 6.

[3][4] DE 15 crosses the Providence Creek into New Castle County and the name becomes Clayton Greenspring Road as it passes through farm fields and woods with some homes.

The route runs through agricultural areas, crossing the Appoquinimink River, and turns north-northeast onto Levels Road.

DE 15 enters the town of Middletown, passing to the west of a residential neighborhood before turning northwest at a roundabout with St. Annes Church Road and Wallasey Drive to remain on Levels Road and reach an intersection with DE 299.

The roadway passes over the US 301 toll road, where it has a ramp for emergency vehicles but no public access, before heading northeast of Appoquinimink High School.

[5] The portion of the route along the DE 6 concurrency west of Clayton and between Alley Mill Road and Caldwell Corner Road in southwestern New Castle County is part of the Harriet Tubman Underground Railroad Byway, a Delaware Byway.

[25] On June 5, 2017, construction began for a roundabout at the junction with DE 10 west of Camden in order to improve safety at the intersection.