Minnesota State Highway 65 is a highway in east-central and northeast Minnesota, which runs from its intersection with Washington Avenue (Hennepin County Road 152) at the north end of downtown Minneapolis and continues north to its northern terminus at its intersection with U.S. Highway 71 in Littlefork near International Falls.

Highway 65 is a four lane expressway between Interstate 694 in Fridley to just north of State Highway 95 at Cambridge.

The route continues as a two-lane road from Cambridge to its northern terminus at Littlefork in northern Minnesota.

State Highway 65 is 273 miles (439 km) in length.

State Highway 65 serves as a north–south route between Minneapolis, Fridley, Blaine, Cambridge, Mora, McGregor, Nashwauk, and Littlefork in east-central and northeast Minnesota.

The roadway is one of three Minnesota state marked highways to carry the same number as an existing U.S. marked highway within the state, the others being Highways 61 and 169.

State Highway 65 begins at the intersection of Washington Avenue (County 152) and 3rd Avenue South at the north end of downtown Minneapolis. Highway 65 is signed locally as 3rd Avenue South in downtown Minneapolis. 3rd Avenue South leads to the Third Avenue (Mississippi River) Bridge and becomes Central Avenue upon crossing the river. After its intersection with Hennepin Avenue, the route becomes Central Avenue NE. Highway 65 is signed locally as Central Avenue NE for this section. Many Minnesota landmarks are located on Central Avenue NE including the Aveda Institute, the Heights Theater, and the National Sports Center. The route remains Central Avenue until separating in Ham Lake, except for a split in Fridley and Spring Lake Park between I-694 and U.S. Highway 10.

The route is a divided highway from Minneapolis to Cambridge, with a 60 MPH speed limit, increasing to 65 MPH speed limit beginning in Ham Lake, just outside of Blaine.

Savanna Portage State Park in Aitkin County is located 11 miles northeast of the junction of Highway 65 and County Road 14 in Shamrock Township near McGregor. The park entrance is located on County Road 14 in nearby Balsam Township. Minnesota DNR website for Savanna Portage State Park - Link

State Highway 65 was authorized in 1934 and 1935. The route was numbered as an extension of old U.S. Highway 65.

By 1940, the route was paved from Minneapolis to just north of McGrath in Aitkin County. By 1949, the route was paved as far north as Libby. By 1953, the route was paved north to its intersection with U.S. Highway 2 at Swan River in Itasca County. Sections of Highway 65 north of U.S. 2 were paved in the 1960s and 1970s. The last section of Highway 65 paved was through the Nett Lake Indian Reservation in 2000.

The expressway section of Highway 65 between I-694 in Fridley to Spring Lake Park was constructed on a new alignment in 1953.

The Highway 65 expressway bypass in Cambridge was completed circa 1993.

A portion of State Highway 65 used to be part of old U.S. Highway 65. U.S. 65 still enters Minnesota from Iowa, but ends now in the city of Albert Lea, where it has a junction with Interstate 35. I-35 and I-35W roughly follow the same route old U.S. 65 used to take from Albert Lea to downtown Minneapolis. Before the freeways were built, the original U.S. 65 had followed Lyndale Avenue between Burnsville and Minneapolis.

In July 2005, a small section of State Highway 65 in downtown Minneapolis, between Washington Avenue and I-35W, was turned back to city maintenance. The southern terminus of State Highway 65 is now at the intersection of Washington Avenue and 3rd Avenue South in downtown Minneapolis. However, the ramps to and from I-35W south of downtown, are still contrarily labeled with the MN-65 shield on the updated mileposts.