The trunkline passes through a mix of farm fields and woodlands, crosses or runs along several rivers and connects several small towns of the southern area of the state.

The westernmost segment runs along divided highway while the easternmost section is a full freeway bypass of Jackson.

In the mid-1920s, the western end was extended to New Buffalo; since then several bypasses of the smaller towns along the highway were added.

The trunkline continues through mixed farm fields and woodlands, running northeastward to Cassopolis and rounding Stone Lake on the southern approach to town.

M-60 turns eastward on State Street, separating from M-62, and leaves town[3][4] while crossing a line of the Canadian National Railway.

East of Jones, the trunkline crosses into St. Joseph County and meets US 131 on the south side of Three Rivers.

The two highways run concurrently northward through a retail business corridor to an intersection with Michigan Avenue.

The business loop turns north at the same intersection where M-60 meets M-86 near the Rocky River crossing.

The trunkline turns north, runs by Fishers Lake and continues out of town through farm fields.

[3][4] South of Athens, M-66 turns northward and M-60 continues around Union City and into southern Calhoun County.

M-60 continues east through farm fields to Tekonsha where it meets Interstate 69 (I-69) northwest of town.

Outside of Jackson, the highway widens out to a full freeway bypass around the west side of the city.

North of this interchange, the highway picks up the Business Loop I-94[3][4] and crosses the Norfolk Southern Railway line in the area.

[9] M-60 was designated with the rest of the original state highway system by July 1, 1919, on a series of roads running between Niles and Jackson by way of Cassopolis, Three Rivers and Tekonsha.

[12][13] M-60 was rerouted around Concord in 1933,[14][15] Tekonsha was bypassed by the MSHD in late 1936,[13][16] and the highway was routed around Union City in 1937.

[26][27] At the end of the 1950s, M-60 was moved to a freeway bypass along the west side of Jackson; the final mile was also designated Bus.

Near the Berrien–Cass county line, the highway passes south of the Jerry Tyler Memorial Airport.

It acted as a "business route" into downtown Concord during its short lifetime after a bypass of town along M-60 was built.