It runs for almost eight miles (13 km) along Gull Road between the northeast side of Kalamazoo and continues through rural areas on the way to Richland.

It had been a part of the state highway system for a century under its previous number until it was given its current designation.

M-343 then turns due east along D Avenue for a short distance before terminating at an intersection with M-89 in the middle of Richland.

[7] Passage of the State Reward Trunk Line Highways Act on May 13, 1913, provided for 3,000 miles (4,828 km) of roadways in a state-financed system.

[14] On January 7, 2019, the City of Kalamazoo accepted jurisdiction over those streets from MDOT, ending their status as state trunklines.