The original M-65 was created by 1919 on a discontinuous series of roads between the Ohio state line and Flint; the two sections were later joined together before the highway was replaced by US 23 in 1926. The current M-65 was created in 1930 in Iosco County. When US 23 near Omer was moved in 1932, M-65 was extended southward to encompass a roadway formerly part of US 23. A second segment in Alpena County was added to M-65 later in the 1930s. A second extension at the end of that decade added another former US 23 segment to the highway. The two sections of M-65 were connected in the late 1940s, and the highway was completely paved by the early 1960s. The National Forest Scenic Byway and National Scenic Byway designations were added in 1988 and 2005 respectively.