Before the Interstate era, M-21 extended across the entire Lower Peninsula, from the junction with
US 31 in Holland near
Lake Michigan east to the
St. Clair River at Port Huron, and crossed into
Canada where the
Blue Water Bridge is currently located. M-21 was designated by July 1, 1919 on a routing from Ionia to Goodells. Along the way, it ran through
Lyons and Pewamo, joining its current routing to Ovid. M-21 continued through Corunna to Lennon and Flint. There it joined its last routing between Flint and the Port Huron area. The highway was extended to Port Huron by 1924, and the west end was extended to Grand Rapids in 1925 along
M-16 (later
US 16). The previous routing through Owosso and Lennon was redesignated as
M-71 at this time when M-21 was shifted along the current routing between the two communities. The 1926 creation of the
United States Highway System led to the extension of M-21 along US 16 to Grand Rapids. From there west, M-21 replaced
M-51 on
Chicago Drive to Holland. The highway was moved to a new routing between Flint and
Lapeer in 1929; the old route was renumbered
M-21A. All in-city portions of M-21 were transferred to state control in 1931 with the passage of the Dykstra Act of 1931 (PA 131 of 1931). A
Bypass M-21 (Byp. M-21) designation was created in the Grand Rapids area in 1945. This designation ran from the corner of 28th Street and Chicago Drive along
Byp. US 16 and
Byp. US 131 on 28th Street. At East Beltline Avenue, Byp. US 131/Byp. M-21 turned north back to M-21. M-21A in Flint was turned over to local control in 1948, decommissioning the number. The Byp. M-21 routing was replaced by M-21 in 1953. The former routing in Grand Rapids became
Bus. M-21 instead. A bypass of
Zeeland opened in 1958, rerouting M-21 around the town. The
I-196 freeway opened through Grand Rapids in 1964, and M-21 was routed along the freeway between Chicago Drive in
Grandville and downtown, using I-96 to complete the connection to its previous routing on Fulton Street. The first freeway segment of M-21 on the east end was built from
Wadhams to Port Huron in 1966. A freeway segment between Flint and Lapeer opened in 1971. M-21 was routed down M-13 to the new freeway where it joined the
M-78 designation from M-13 east. The section of M-21 formerly between M-13 and
Bus. M-54 was redesignated M-56. The M-78 designation was replaced by
I-69 in 1973 after I-69 was extended north from
Charlotte. The 1974 completion of I-196 meant the truncation of M-21 to end in Grand Rapids. At the time, M-21 was extended along Fulton Street to the East Beltline, and the business loop was truncated into a spur route redesignated
BS I-196. The remaining segment of freeway connecting Flint with Port Huron opened in 1984 as I-69, and M-21 was shortened to Flint. M-56 was replaced by M-21 at this time as well. The former M-21 in Port Huron became
BL I-69, and the remainder was turned back to local control. ==Major intersections==