U.S. Route 380 (US 380) is an east–west United States highway. The highway's eastern terminus is in Greenville, Texas at an intersection with Interstate 30, of which the easternmost 3–4 miles are concurrent with US 69 in a loop around the west and south sides of Greenville. Its western terminus is at San Antonio, New Mexico, south of Socorro at an intersection with Interstate 25. It intersected with its parent, U.S. Route 80, at Cisco until 1971, when it was rerouted along the former SH 24 from that highway's western terminus near Old Glory to Greenville. Former U.S. Route 380 from Cisco to near Old Glory became an extension of SH 6. The highway no longer connects to any x80 route. US 380 passes through some of the far northern suburbs of the Dallas/Fort Worth Metroplex, including Denton, Frisco, McKinney and Princeton. The portion in Texas from the New Mexico state line to Jayton was SH 84 before 1939. Its spur, SH 84A, went from Jayton to Aspermont, until 1930, when it became SH 161.

Greenville is a city in Hunt County, Texas, United States, approximately 50 miles (80 km) northeast of Dallas, Texas and 52 miles (84 km) northwest of Canton, Texas. It is the county seat and largest city of Hunt County. As of the 2020 census, the city population was 28,164.