Upon reaching downtown Wilmington, the route intersects Interstate 95 (I-95)/US 202 and DE 4 before continuing to the eastern terminus.

The ferry was discontinued in 1949 and the eastern terminus of DE 48 was cut back to its current location by 1952.

The route widens into a four-lane divided highway before crossing the Wilmington and Western Railroad at-grade and Red Clay Creek.

The two routes head southeast as a four-lane undivided road, crossing Chestnut Run and passing through residential and commercial areas.

Following this intersection, the route crosses over CSX's Philadelphia Subdivision railroad line on a bridge.

DE 48 continues into downtown Wilmington, where it crosses under a viaduct carrying I-95/US 202, with ramp connections to and from the southbound direction of I-95/US 202 via Jackson Street, which parallels I-95/US 202 to the west.

[3][4] Upon crossing under I-95/US 202, a westbound ramp to I-95/US 202 complements the eastbound direction of DE 48, with the road becoming Martin Luther King Jr. Boulevard, a six-lane divided highway.

The one-way pair continues further into the downtown, passing to the south of the Orlando J. George, Jr. Campus of Delaware Technical Community College, and runs a short distance to the north of Amtrak's Northeast Corridor railroad line.

DE 48 reaches its eastern terminus at an intersection with the northbound direction of US 13 Bus., which follows Walnut Street, west of the Wilmington Transit Center serving DART First State buses.

In addition, the route continued through Wilmington on Lincoln Street, Fourth Street, and Christina Avenue to the ferry across the Delaware River to Penns Grove, New Jersey, which linked DE 48 to Route 48 in New Jersey.