In the years immediately preceding the creation of the Interstate Highway System, US 16 was shifted from older roads to newer freeways.

The original pathway along the Grand River Avenue corridor was an Indian trail, a footpath used by the native population.

In Detroit, Grand River is one of five major avenues (along with Woodward, Michigan, Gratiot, and Jefferson) planned by Judge Augustus Woodward in 1805 that extended from Downtown Detroit in differing radial directions; Grand River Avenue extends northwesterly from the city's downtown.

At the time of its decommissioning, US 16 started its run through Michigan at the Grand Trunk Western Railroad docks in Muskegon.

(Later, the I-96 and I-196 designations west of Grand Rapids would be flipped,[5] but at the time leading up to US 16's decommissioning in the state of Michigan, this had not yet been approved.

The freeway turned more directly east in Nunica past the eastern terminus of M-104, and continued through more mixed forest and grassland terrain to serve the communities of Coopersville and Marne.

[3] As the freeway approached Kent County, it met the western terminus of M-11 which was the former routing of US 16 through the Grand Rapids metropolitan area.

Grand River Avenue carried the highway past the Capital City Airport and east to Larch Street, where US 16 turned south along US 27 north of downtown Lansing.

Grand River Avenue through East Lansing follows a tree-lined boulevard that forms the division between the campus of Michigan State University to the south and the rest of the city to the north.

In the approach to Brighton, Grand River Avenue passes through rural southeast Michigan lake country.

[11] A ten-year project to construct a plank road between Detroit and Howell was authorized in 1820 along the Grand River Trail.

[14] The opening of the Erie Canal in New York in 1826 brought new settlers to the Great Lakes region, and to the future state of Michigan.

[15] The road branched into two at Rouge (now Redford); the southern branch roughly followed the modern route of Grand River Avenue and the northern route ran by way of Pontiac along Woodward Avenue and the modern M-21 to the north of the Lansing area.

[18] The early travelers plied the road in wagons pulled by oxen or horses, and drivers charged between four and seven cents a mile (equivalent to $1.08–1.89/mi in 2023[19]).

[22] These improvements included removing brush and debris and the construction of bridges across the Rouge, Shiawassee, Red Cedar and Grand rivers.

[24] An economic panic in 1837 drove settlers from New York to Michigan; these were the travelers who followed the Grand River Road.

The former routing through Downtown Lansing on Michigan Avenue became part of M-39 and the section north of Grand Ledge was eventually redesignated M-100.

Today the roadway remains the "Main Street" of over a dozen Michigan cities and a scenic route through one of the state's most populated corridors.

In 1995, major reconstruction work along Grand River Avenue in East Lansing uncovered rotting logs, buried about 2 feet (0.61 m) below the present grade, that had been used as underlayment for the plank road surface in a low, swampy area.

[52] In 2004, the state transferred several blocks at the eastern end of Grand River Avenue to the City of Detroit.

The group "Lansing for Cesar E. Chavez" was raising funds to rename the section between Oakland and Pine streets in Old Town.

[55] The renaming proposal was even mentioned as a way to untangle a maze of different branches of Grand River Avenue running through Old Town.

One shop owner said she would have $10,000 in costs associated with a name change, adding, "I think there's many beautiful ways to honor such an incredible man.

[57] The compromise solution reached in August 2010 was to rename lot 56, where Old Town holds festivals, to Cesar Chavez Plaza.

[58] Born in Grand Rapids in 1884, Arthur H. Vandenberg was appointed to the United States Senate upon the death in office of Woodbridge N. Ferris in 1928.

Vandenberg, a Republican, served as a member of the "isolationist bloc", and was an active opponent of the New Deal policies of Franklin D. Roosevelt.

He also worked to secure passage of the Marshall Plan and helped to establish the North Atlantic Treaty Organization.

The following year, the Michigan Legislature dedicated the length of US 16 from Muskegon to Detroit as the Arthur Vandenberg Memorial Highway by enacting Public Act 70 of 1952.

For a period from the 1930s through the 1950s, the highway used a few blocks of Washington Boulevard to connect between Grand River and Michigan avenues on its route through Detroit to its terminus at Cadillac Square.

[49][66] The original plans for I-96 called for it to replace US 16 and to run parallel to Grand River Avenue all the way from Farmington into downtown Detroit.