West of DE 1, the route serves as part of a connection between the Baltimore–Washington Metropolitan Area and the Delaware Beaches.

DE 16 begins at the Maryland border in the community of Hickman in Kent County, where the road continues west into that state as MD 16.

From the state line, the route heads east on two-lane undivided Hickman Road, passing through a mix of farmland and woodland with some homes.

The road crosses Marshyhope Creek in the community of Adamsville and enters Sussex County, curving to the southeast.

DE 16 soon becomes undivided again and continues east through agricultural areas and woods with some residences, crossing Toms Dam Branch and running through the community of Owens.

In Ellendale, DE 16 runs past several homes, crossing the Delmarva Central Railroad's Indian River Subdivision line at-grade.

The route heads through woodland and farms, running immediately to the north of the Delmarva Central Railroad's Milton Industrial Track line.

The road intersects DE 1 and passes north of a golf course before it runs through a mix of farms and woods with some homes.

In March 2021, five virtual workshops on the study were held to present collected data and gather input from the public.

[17] On June 21, 2022, a groundbreaking ceremony was held to mark the beginning of construction of an interchange with DE 1 east of Milton, with Governor John Carney, DelDOT secretary Nicole Majeski, and state and local officials in attendance.