The route runs from River Road and Oak Orchard Avenue on the Indian River Bay in Oak Orchard north to an intersection with DE 1 north of Milton.

Along the way, DE 5 passes through rural areas along with the communities of Long Neck, Harbeson, and Milton.

The road continues through a mix of farms and woods with some housing developments, passing northeast of the Nanticoke Indian Museum before coming to an intersection with DE 24.

The road heads north through residential and commercial development with some fields as it enters the Long Neck area, where it intersects DE 23.

In Harbeson, DE 5 heads past homes and crosses the Delmarva Central Railroad's Lewes Industrial Track line before it passes east of an Allen Harim Foods chicken plant and intersects US 9/DE 404 near businesses.

[3][4] Past this intersection, the road runs north through more rural land before curving northwest.

Farther northwest, the route runs along the western border of the town of Milton as it passes west of residential development before reaching a junction with Shingle Point Road/Chestnut Street.

The route turns north again and comes to an intersection with the southern terminus of the DE 5 Alt.

DE 5 continues north on Union Street Extended, passing through agricultural areas with some woods and homes.

is a 3.8-mile-long (6.1 km) alternate route of DE 5 that bypasses the town of Milton.

The route travels west from DE 5 south of Milton along two-lane undivided Sand Hill Road through areas of farms and woods with some homes.

The route turns north to join DE 30 on Gravel Hill Road, crossing an abandoned railroad grade just east of the terminus of the Delmarva Central Railroad's Milton Industrial Track line.