The M-121 designation has been used twice before in the state. The first was for a former routing of US Highway 2 (US 2), and the second was for a connection between I-69, I-75/US 23 and Bishop International Airport in the Flint area. Since 2007, M-121 has been used for a portion of the former M-21 in Ottawa County, which was formerly designated as state-maintained "Old M-21". Future plans will reconfigure a section of the current highway from four lanes divided to four lanes undivided.