U.S. Route 65 is a north–south United States highway in the southern and midwestern United States

United States

The United States of America is a federal constitutional republic comprising fifty states and a federal district...

. The southern terminus of the route is at U.S. Route 425

U.S. Route 425

U.S. Route 425 is a north–south United States highway, first commissioned in 1989. Its route number is a "violation" of the usual AASHTO numbering scheme, as it comes nowhere near its implied "parent", U.S. Route 25....

 in Clayton, Louisiana

Clayton, Louisiana

Clayton is a town in northern Concordia Parish, Louisiana, United States. The population was 858 at the 2000 census. Cotton is a principal commodity in the area. Clayton is located on the Tensas River, important for fishing and boating, promoted through a U.S. Army Corps of Engineers-maintained...

. The northern terminus is at Interstate 35

Interstate 35

Interstate 35 is a north–south Interstate Highway in the central United States. I-35 stretches from Laredo, Texas, on the U.S.-Mexico border to Duluth, Minnesota, at Minnesota Highway 61 and 26th Avenue East. Many interstates used to have splits or spurs indicated with suffixed letters , but I-35...

 just south of Interstate 90

Interstate 90

Interstate 90 is the longest Interstate Highway in the United States at . It is the northernmost coast-to-coast interstate, and parallels US 20 for the most part. Its western terminus is in Seattle, at Edgar Martinez Drive S. near Safeco Field and CenturyLink Field, and its eastern terminus is in...

 in Albert Lea, Minnesota

Albert Lea, Minnesota

Albert Lea is a city in and the county seat of Freeborn County in the southeastern part of the U.S. state of Minnesota. The population was 18,016 at the 2010 census....

. Parts of its modern route in Iowa and historic route in Minnesota follow the old Jefferson Highway

Jefferson Highway

The Jefferson Highway was an automobile highway stretching through the central United States from New Orleans, Louisiana, to Winnipeg, Manitoba, Canada. The Jefferson Highway was replaced with the new numbered US Highway system in the late 1920s...

.
U.S. 65 begins in Clayton, La. In Tallulah

Tallulah, Louisiana

Tallulah is a city in and the parish seat of Madison Parish, Louisiana, United States. The population was 9,189 at the 2000 census...

, it intersects Interstate 20

Interstate 20 in Louisiana

Interstate 420 was to be a bypass of Monroe, Louisiana. Initially proposed in the late 1950s, this route was to have been only two lanes wide at a cost $29 million with a projected 2,500 to 3,000 ADT in 1964. The project was effectively canceled on October 12, 1964, when then Louisiana...

, and approximately 30 miles north of this intersection it enters Arkansas

Arkansas

Arkansas is a state located in the southern region of the United States. Its name is an Algonquian name of the Quapaw Indians. Arkansas shares borders with six states , and its eastern border is largely defined by the Mississippi River...

.
US 65 enters the southeast corner of Arkansas just north of Gassoway, Louisiana.