From the southern terminus, DE 141 heads northwest on Basin Road, a four-lane divided highway.

The road passes to the east of William Penn High School and continues past suburban homes and businesses.

The road comes to an interchange with I-95 (Delaware Turnpike) and the southern terminus of I-295, at which point US 202 splits from DE 141 by continuing north along I-95.

Past this interchange, DE 141 widens to six lanes and has a southbound exit and entrance for South James Street and Old Airport Road before the median narrows.

The freeway comes to a viaduct that crosses the Christina River into the town of Newport, where it heads near industrial areas and passes over Amtrak's Northeast Corridor railroad line.

[4][5] In Newport, the route has an interchange with DE 4, at which point it narrows to four lanes and curves northwest with North James Street serving as a frontage road on both sides.

The freeway widens back to six lanes and heads into a below-grade alignment that cuts through residential neighborhoods, leaving Newport.

Following this interchange, the six-lane freeway rises to ground level and passes to the west of commercial development before coming to a bridge over CSX's Philadelphia Subdivision railroad line.

Following this intersection, the route heads north between the Ferris School to the west and DuPont's Chestnut Run Plaza research facility to the east.

The roadway curves northeast and passes under an East Penn Railroad line before coming to a partial cloverleaf interchange with DE 52 in Greenville.

[4][5] Past this intersection, DE 141 continues east as four-lane divided Barley Mill Road, heading into wooded areas.

The route becomes a two-lane undivided road as it passes to the south of the Hagley Museum and Library before crossing over the Brandywine Creek valley on the Tyler-McConnell Bridge.

Past the bridge, DE 141 turns northeast onto four-lane undivided Powder Mill Road, forming the northwestern boundary of the DuPont Experimental Station.

The road widens into a divided highway and runs between the Nemours Mansion and Gardens to the east and the DuPont Country Club to the northwest.

The route passes to the west of Nemours Children's Hospital, Delaware before coming to a bridge over Rockland Road.

[12] In 1927, plans were made to replace the grade crossing at the Pennsylvania Railroad line (now Amtrak's Northeast Corridor) in Newport with an underpass under the tracks.

[2][3] In 1954, plans were made to replace the intersection with US 13/US 40/US 202 in Basin Corner with a modified cloverleaf interchange in an effort to reduce traffic congestion.

The project reconstructed the bridges that carry DE 141 over I-95 and added safety improvements to the interchange ramps.