U.S. Route 52

U.S. Route 52 is a United States highway that runs across the northern, eastern and southeastern regions of the United States. Contrary to most other even-numbered U.S. Highways, US 52 primarily follows a northwest–southeast route, and is signed north–south or east–west depending on the local orientation of the route.

The highway's northwestern terminus is at Portal, North Dakota, on the Canadian border, where it continues as Saskatchewan Highway 39. The southeastern terminus of US 52 is in Charleston, South Carolina, at Number 2 Meeting Street and White Point Gardens along the Charleston Harbor.

US 52 is one of five U.S. highways to cross the Mississippi River more than once. It crosses the river three times: at Minneapolis via the Dartmouth Bridge, at St. Paul by the Lafayette Bridge, and between Iowa and Illinois by the Savanna–Sabula Bridge. The others are U.S. Route 61, which crosses the Mississippi four times, U.S. Route 169, which crosses three times, and U.S. Route 2 and U.S. Route 67, which each cross twice.