In between the trunkline runs through seven counties of the southern part of the Lower Peninsula mostly through rural farm fields and small communities.

Additional changes made during the 1960s rerouted M-50 to replace its business loop until the highway was shortened to its present western terminus south of Lowell.

The highway proceeds south along with Alden Nash Avenue and turns east on 92nd Street through farms and fields in the rural southeastern corner of the county.

From there, the road continues in its southeasterly path along Clinton Trail through the northeast part of Eaton County as it runs through fields to Charlotte.

Just prior to entering the city, the road bends to the south and near the middle of town it has a junction with M-79 and Business Loop I-69 (BL I-69).

The road then proceeds south through the northern side of the city before turning east on Michigan Avenue as it heads towards downtown.

The road serves as main street for downtown Brooklyn as well as the primary thoroughfare for drivers headed to Michigan International Speedway.

Prior to reaching its interchange with US 23, the highway passes to the south of Cabela's,[3][4] a 225,000-square-foot (20,900 m2) outdoor sports retailer in Dundee.

[6] After leaving town, the trunkline continues to the southeast, running to the south of the River Raisin, through rural areas as South Custer Road before entering the outskirts of Monroe where it finally ends its journey at a junction with US 24 (Telegraph Road) a few miles inland from Lake Erie.

[7] The only sections of M-50 that have been listed on the National Highway System (NHS) are the two US 127 concurrencies in the Jackson area and the connection between them through downtown.

[9] When the state highway system was first signed in 1919,[10] M-50 started at an intersection with M-23 (present-day US 12) in Cambridge Junction, south of Brooklyn.

[11] By the end of 1927, M-50 underwent a major lengthening as its western terminus was extended through Jackson to Eaton Rapids, Charlotte, and Vermontville before intersecting M-39 just east of Woodbury.

M-50 then ran concurrently with US 16 into Grand Rapids where it turned to the west and traveled through Allendale before terminating at a junction with US 31 in Agnew.

[17][18] In 1961, when the I-96/US 16/M-50 freeway was extended to the northwest in Grand Rapids, the old M-50 routing around the city became M-11 and M-50 was returned to its former alignment along Lake Michigan Drive and Fulton Street, supplanting Bus.

The state trunkline highway was created when M-50 was rerouted to follow 28th Street and Wilson Avenue around the south and west sides of the city in 1953.

[19][20] The highway followed Lake Michigan Drive (now M-45) from the Standale neighborhood of Walker easterly to Fulton Street in Grand Rapids.