In the U.S. state of North Carolina, U.S. Route 220 (US 220) is a north–south highway that connects the cities of Rockingham, Asheboro and Greensboro, in the central piedmont.

Though the highway is commonly known as "US 220" throughout the state, the highway does have other known names it uses locally in areas.

Established in 1935 when US 220 was extended south from Virginia; it replaced: US 311/NC 77 from the state line to Madison, US 411/NC 704 from Madison to Greensboro, US 411/NC 70 from Greensboro to Candor, US 411/NC 170 from Candor to Norman, and US 15/NC 75 from Norman to Rockingham.

By 1939, US 220 was realigned west of Seagrove, leaving Old US Highway 220 and an extension of NC 705. By 1963, US 220 bypassed Madison and Mayodan, the old route through the towns became US 220 Business. Between 1964-1966, Stoneville was bypassed to its west. Between 1967-1968, US 220 we realigned west, onto new freeway, of Asheboro, leaving US 220 Business. In 1970, US 220 was rerouted in Greensboro, from Randleman Road it overlapped with Interstate 85 then onto O. Henry Boulevard (in concurrency with US 29) going north till Wendover Avenue, then west to Battleground Avenue; the original alignment through downtown Greensboro became unnumbered.

In the 1970s, US 220 was continuously moved onto new freeway, bypassing Randleman and Level Cross. Also, at some point during the decade, US 220 was extended south to its current terminus with US 1, leaving behind Ellerbe Road in Rockingham.

In 1980, US 220 was moved onto new freeway between Steeds and Emery, it's old alignment became US 220 Alternate. Between 1981-1983, US 220 moved onto new freeway from Level Cross to Interstate 85, leaving an unnumbered Randleman Road.

In 1995, US 220 was moved onto new freeway between Interstate 85 to Interstate 40. In May, 1997, US 220 was moved onto new freeway between Ether and NC 134; it not only extended US 220 Alternate over the old alignment, but also became the first section of both Interstate 73 and Interstate 74.

On January 7, 2008, US 220 was moved onto new freeway between Emery to south of Ellerbe, leaving its old alignment another extension of US 220 Alternate.

The Western Rockingham Bypass, from the US 74/US 74 Bus. interchange to US 220 Alt near Ellerbe. Currently all right-of-way purchases have been completed along the proposed route, with construction beginning in 2012 on upgrading US 220 north of Rockingham. The remaining sections of the new bypass is currently scheduled to begin construction in late 2017; however, it is subject to reprioritiation.

Widen US 220 to multi-lanes, from Horse Pen Creek Road, in Greensboro, to Winfree Road, in Summerfield. Funded, with construction expected to be completed December, 2016.

New freeway, for Interstate 73, from NC 68, near PTI Airport, to NC 68, in Rockingham County. US 220 is included, north of Summerfield, with this project. Currently all right-of-way purchases have been completed along the proposed route, with construction scheduled to begin April, 2014.