U.S. Route 13 is the main north–south highway in the U.S. state of Delaware. It traverses the entire length of the state from the Maryland border in Delmar, Sussex County to the Pennsylvania border in Claymont, New Castle County. U.S. Route 13 connects many important cities and towns in Delaware, including Wilmington, Dover, and Seaford. It was the main route between Wilmington and Dover and a part of the main route from Wilmington to the Delaware beaches until the Delaware Route 1 turnpike was completed. It continues to serve as the main route from Delaware to points south, such as Salisbury, Maryland and Norfolk, Virginia. The entire length of U.S. Route 13 in Delaware is a divided highway with the exceptions of the segment through Wilmington and parts of Philadelphia Pike in Claymont. Between Wilmington and the Kent/Sussex County border, U.S. Route 13 in Delaware is known as Dupont Highway or Dupont Parkway. In Sussex County, the route is known as Sussex Highway.

U.S. Route 13 crosses into Delaware in the border town of Delmar. At the state line, U.S. Route 13 intersects Delaware/Maryland Route 54, which follows the state line for several miles. U.S. Route 13 continues north, intersecting Delaware Route 30 between Laurel and Delmar, and then Delaware Route 24 and U.S. Route 9 in Laurel. In Seaford, U.S. Route 13 shares a brief concurrency with Delaware Route 20 on the eastern end of town. U.S. Route 13 continues north and intersects Delaware Route 18 in Cannon, just south of Bridgeville. In Bridgeville, U.S. Route 13 Business loops off of U.S. Route 13 through the central area of town. Also in Bridgeville, U.S. Route 13 shares a concurrency with Delaware Route 404, which bypasses Bridgeville. North of the Delaware Route 404 concurrency, U.S. Route 13 continues north to Greenwood, where it intersects Delaware Route 16 and Delaware Route 36.

U.S. Route 13 continues north into Kent County, passing through the small town of Farmington. It then continues north to Harrington, home of the Delaware State Fair, where it intersects Delaware Route 14 Truck just before the Delaware State Fairgrounds, forming a concurrency with that route. It crosses Delaware Route 14 in the center of Harrington, where the truck route ends. In Harrington, U.S. Route 13 splits into two one-way roads with businesses in the median. After Harrington, U.S. Route 13 continues north, intersecting Delaware Route 12 in Felton. It then passes through Canterbury, where it crosses Delaware Route 15 and also where an alternate route, U.S. Route 13 Alternate, branches off to serve Woodside and Camden, returning to U.S. Route 13 north of Camden. U.S. Route 13 intersects Delaware Route 10 Alternate in Woodside and Delaware Route 10 in Camden.

U.S. Route 13 then enters the capital city of Delaware, Dover. Near Rodney Village another U.S. Route 13 Alternate branches off to pass through downtown Dover. U.S. Route 13 intersects the Puncheon Run Connector, which provides a connection to Delaware Route 1 that is mainly used for traffic that follows U.S. Route 13 south of Dover. U.S. Route 13 then intersects Bay Road, formerly U.S. Route 113 until it was truncated to Milford in 2004, near the State Capitol Complex. After that intersection comes Delaware Route 8 and after that U.S. Route 13 reconnects with Alt U.S. 13 near Dover Downs. U.S. Route 13 then continues through commercial North Dover passing Delaware State University and Dover Mall. At the north end of Dover, U.S. Route 13 features an interchange with Delaware Route 1.

Past Dover, U.S. Route 13 continues north to Cheswold and intersects Delaware Route 42. It then moves on northward to Smyrna, where it features interchanges with Delaware Route 1 on both sides of town and an intersection with Delaware Route 6 and Delaware Route 300 in the center of town.

U.S. Route 13 then enters Delaware's most populous county, New Castle County. It heads north from Smyrna, intersecting Delaware Route 71 near Townsend. It heads north to the town of Odessa, where it intersects Delaware Route 299. U.S. Route 13 then continues into farmland that is becoming built up as the Wilmington area pushes southward. It meets Delaware Route 896 in Boyds Corner. U.S. Route 13 then reaches the St. Georges Bridge, which carries it over the Chesapeake and Delaware Canal. Just south of the bridge, U.S. Route 13 features right-in/right-out connections to Delaware Route 1, which crosses the canal on the Chesapeake and Delaware Canal Bridge.

North of the St. Georges Bridge, U.S. Route 13 enters a more urban atmosphere. It meets Delaware Route 72 near Delaware City. U.S. Route 13 turns west on Delaware Route 72 for a brief time and then follows the Delaware Route 1 turnpike to Tybouts Corner. The construction of Delaware Route 1 displaced a section of the original U.S. Route 13, with a segment becoming partly abandoned with the northbound lanes closed and the southbound lanes converted to a two-lane frontage road and the southernmost segment becoming a southward extension of Delaware Route 7.

U.S. Route 13 splits from Delaware Route 1 in Tybouts Corner. It intersects Delaware Route 71 for a second time at the Delaware Route 1 interchange. U.S. Route 13 continues north through suburban development and meets U.S. Route 40 in State Road. The two highways share a concurrency up to the Interstate 295 interchange in Wilmington Manor, where U.S. Route 40 heads east on Interstate 295 towards the Delaware Memorial Bridge. Along this concurrency, U.S. Route 40 is only mentioned along signs on cross roads and on overhead guide signs, with reassurance markers only mentioning U.S. Route 13. The 13/40 concurrency intersects Delaware Route 273 in Hares Corner and then it passes by the New Castle Airport. At the north end of the airport, there is an interchange with U.S. Route 202 and Delaware Route 141. US 13 and US 40 continue concurrent through Wilmington Manor until U.S. Route 40 turns east onto I-295.

North of Interstate 295, U.S. Route 13 continues north to an interchange with Interstate 495 just south of the city limits of Delaware's largest city, Wilmington. Just north of the I-495 interchange, U.S. Route 13 Business splits off from U.S. Route 13 and passes through the heart of Wilmington while U.S. Route 13 bypasses the city to the east. U.S. Route 13 enters Wilmington on Heald Street. Just south of the Christina River, U.S. Route 13 meets Delaware Route 9 (New Castle Avenue). Delaware Route 9 follows U.S. Route 13 over the Christina River on a drawbridge and then heads toward downtown Wilmington on Fourth Street. U.S. Route 13 turns north on the one-way pair of Church Street northbound and Spruce Street southbound. Just south of the Brandywine Creek, U.S. Route 13 becomes two-way Northeast Boulevard and continues northeast out of Wilmington.

U.S. Route 13 then continues to Edgemoor, where it meets Delaware Route 3, which provides access to Interstate 495. U.S. Route 13 takes on the name Governor Printz Boulevard, and closely parallels Interstate 495, the Amtrak Northeast Corridor, and the Delaware River north to Claymont. When U.S. Route 13 reaches Claymont, it turns away from the Delaware River and re-intersects U.S. Route 13 Business. U.S. Route 13 then heads north on Philadelphia Pike and features another interchange with Interstate 495. It then continues north through and industrial environment and intersects Delaware Route 92 near the Pennsylvania border. U.S. Route 13 then continues north into Marcus Hook, Pennsylvania, where it passes through a large Sunoco refinery.

Plans for the Dupont Highway spanning the north–south length of Delaware existed as early as 1908 when Thomas Coleman du Pont envisoned a divided highway with trolley lines and separate paths for horse-drawn vehicles. However, only a two-lane road was completed in 1924. In 1933, the Dupont Highway was widened into a divided highway between Wilmington and Dover, and it became the first such highway in the world. U.S. Route 13 would utilize this highway between Wilmington and Dover with U.S. Route 113 following the Dupont Highway between Dover and the Maryland border.

U.S. Route 13 was designated in Delaware in 1926 with the creation of the U.S. Highway System. The original routing ran from the Maryland border in Delmar north to Dover. It then continued north, following the Dupont Highway between Dover and Wilmington, Market Street through Wilmington, and the Philadelphia Pike between Wilmington and the Pennsylvania border.

Throughout the 20th century, several changes have been made to US 13. The St George's Bridge, which carries US 13 across the C&D Canal, opened in 1942. In the 1950s, dualized bypasses of Dover and the corridor from north of Seaford to the Maryland border in Delmar were created. By the 1960s, the remainder of US 13 between Dover and the Maryland border was dualized. In the 1970s, US 13 was rerouted to bypass Wilmington, replacing a U.S. Route 13 Alternate that was created in 1940. The original alignment of US 13 through Wilmington became U.S. Route 13 Business.

Toward the second half of the 20th century, traffic volumes on US 13 between Wilmington and Dover became a headache from beach traffic in the summer months as well as from through traffic in general. In the 1950s, plans were made for a bypass from Dover to Frederica, and in the 1960s, plans were made for a westerly bypass of Dover. Nothing came from these plans. In the 1970s, plans were made for a turnpike between Wilmington and Dover. This road would be built between 1991 and 2003 as the Korean War Veterans Memorial Highway (Delaware Route 1). A connector between DE 1 and US 13, the Puncheon Run Connector, was built in 2001 to provide a connection between the DE 1 turnpike and US 13 mainly used by through traffic following US 13 to points south of Dover.

The construction of Delaware Route 1 resulted in a few changes to US 13. The construction of the Smyrna-Odessa segment resulted in a realignment of US 13 south of Odessa. The route was moved a bit to the east of its original alignment in order to make room for DE 1. The southbound lanes would become a two-lane frontage road called Harris Road from just south of the Appoquinimink River to Noxontown Road with a new two-lane road being built between Noxontown Road and Pine Tree Corner Road. Another segment of US 13 was displaced near Red Lion with the construction of a segment of Delaware Route 1 that was completed in 1995. The segment of highway north of the Delaware Route 7 intersection was cut off by the new highway. The northbound lanes were abandoned, and the southbound lanes became a two-lane road. US 13 was realigned to follow DE 1 between the Delaware Route 72 interchange and Tybouts Corner and DE 7 was extended south on the former alignment of US 13 between the partly abandoned segment and DE 72. The construction of this segment of Delaware Route 1, which included the Chesapeake and Delaware Canal Bridge, prompted for a planned demolition of the 50-year-old St. Georges Bridge, which carries US 13 across the Chesapeake and Delaware Canal. However, residents of St. Georges opposed the demolition because it would cut their town in half. Instead, the bridge was rehabilitated. Between 1995 and 1998, a temporary Bypass US 13 followed DE 1 across the new Chesapeake and Delaware Canal Bridge.