Interstate 75 is the main thoroughfare between Detroit, Flint, and Saginaw extending north to Sault Sainte Marie and providing access to Sault Sainte Marie, Ontario. The expressway crosses the Mackinac Bridge between the Lower and Upper Peninsulas. Branching highways include I-275 and I-375 in Detroit; I-475 in Flint; and I-675 in Saginaw. Interstate 69 enters the state near the Michigan-Ohio-Indiana border, and it extends to Port Huron and provides access to the Blue Water Bridge crossing into Sarnia, Ontario. Interstate 94 enters the western end of the state at the Indiana border, and it travels east to Detroit and then northeast to Port Huron and ties in with I-69. I-194 branches off from this freeway in Battle Creek. I-94 is the main artery between Chicago, Illinois and Detroit.

Interstate 96 runs east-west between Detroit and Muskegon. I-496 loops through Lansing. I-196 branches off from this freeway at Grand Rapids and connects to I-94 near Benton Harbor. I-696 branches off from this freeway at Novi and connects to I-94 near St Clair Shores.

U.S. Route 2 enters Michigan at the city of Ironwood and runs east to the town of Crystal Falls, where it turns south and briefly re-enters Wisconsin northwest of Florence. It re-enters Michigan north of Iron Mountain and continues through the Upper Peninsula of Michigan to the cities of Escanaba, Manistique, and St. Ignace.

Along the way, it cuts through the Ottawa and Hiawatha National Forests and follows the northern shore of Lake Michigan. Its eastern terminus lies at exit 344 of I-75, just north of the Mackinac Bridge. This is generally regarded as the main route through the Upper Peninsula, although some prefer to travel on M-28 as it tends to save time (U.S. 2 hugs the Lake Michigan shoreline for much of its length.)

Major bridges include the Ambassador Bridge, Blue Water Bridge, Mackinac Bridge, and International Bridge. Michigan also has the Detroit-Windsor Tunnel crossing into Canada.

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