From the state line, the route heads east on two-lane undivided Sudlersville Road through agricultural areas and woods with some homes.

A short distance after the state line, the road intersects the western terminus of DE 44 at Everetts Corner.

DE 300 continues east-northeast through rural areas, passing through the community of Downs Chapel and crossing Jordan Branch.

At this point, the road becomes Main Street and passes homes along with a few businesses, intersecting DE 42 in the center of town.

[3][4] Past Kenton, DE 300 continues northeast on Wheatleys Pond Road, passing through more farm fields, some woodland, and residences.

The two routes pass a mix of homes and businesses before gaining a center left-turn lane past the Main Street junction and entering a commercial area in the northern part of Smyrna as East Glenwood Avenue.