US 65 south of Clinton.
Highway 65 between Leslie and Harrison
US 65 runs south near Grady
Natchez-Vidalia Bridge over Mississippi River
U.S. Route 65 in Springfield, Missouri.
US 65 crosses the Des Moines River south of Pleasant Hill

The city of Natchez, Mississippi, lies on the opposite bank of the river, connected by the Natchez–Vidalia Bridge, carrying U.S. Routes 65, 84, and 425.

- Vidalia, Louisiana

At its creation in 1926, U.S. 65 ran from St. Paul, Minnesota to Vidalia, Louisiana.

- U.S. Route 65
US 65 south of Clinton.

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Natchez, Mississippi

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County seat and only city of Adams County, Mississippi, United States.

County seat and only city of Adams County, Mississippi, United States.

Steamboat operating out of New Orleans
House on Broadway Street, Eidelweiss

Located on the Mississippi River across from Vidalia in Concordia Parish, Louisiana, Natchez was a prominent city in the antebellum years, a center of cotton planters and Mississippi River trade.

U.S. 425 runs north from Natchez after crossing the Mississippi, connecting Ferriday with Clayton, at which point U.S. 65 follows the west bank of the Mississippi, connecting to Waterproof north to St. Joseph, Newellton, and Tallulah, Louisiana.