M-66 is a four-lane highway that connects with State Road 9 (SR 9) at the Indiana state line in southern St. Joseph County. The highway runs north to Sturgis through farm land where it turns east through town running concurrently with US 12 on Chicago Road. As it leaves Sturgis to the north it crosses a branch of the Michigan Southern Railroad, and it becomes a two-lane surface highway along Nottawa Street. The highway runs near several small lakes and crosses the Nottawa Creek before meeting M-86. The two highways run north–south concurrently for about along the Nottawa–Colon township line. Farther north, M-66 crosses the St. Joseph River and meets M-60. M-60/M-66 run together to the east, turning northeasterly in Leonidas running parallel to Nottawa Creek and crossing into the northwest corner of Branch County. M-60 and M-66 separate west of Union City, and M-66 turns north into Calhoun County.