From the western terminus, DE 42 heads southeast on two-lane undivided Blackiston Road.

In Kenton, the route crosses an abandoned railroad line and passes residences and a few businesses, intersecting with DE 300 in the center of town.

[3][4] Past Kenton, DE 42 heads to the east-southeast on Seven Hickories Road into farmland with woods and residences, crossing Pinks Branch.

DE 42 reaches an intersection with US 13 on the eastern edge of Cheswold at Bishops Corner.

Farther east, the route turns southeast into marshland adjacent to the Leipsic River, crossing Dyke Branch.

[1][4] DE 42 has an annual average daily traffic count ranging from a high of 7,654 vehicles at the eastern border of Cheswold to a low of 536 vehicles at the eastern terminus at DE 9.