The eastern terminus was moved to its current location in 1965 when US 113 (now DE 1) was routed to bypass Frederica to the east.

DE 12 begins at the Maryland border in the community of Whiteleysburg, with the road continuing west into that state as MD 314.

From the state line, the route heads southeast on two-lane undivided Whiteleysburg Road briefly before turning northeast onto Whites Lane.

The route intersects Sandtown Road before it curves east and enters the town of Felton.

The road name changes to East Main Street and it comes to an intersection with US 13 near businesses on the eastern edge of Felton.

[3][4] Upon leaving Felton, the route becomes Midstate Road and continues through agricultural areas with some woods and homes, passing to the north of the geographic center of Delaware.