Interstate 69 (I-69) is a part of the Interstate Highway System that currently runs from Indianapolis, Indiana, to the US–Canadian border at Port Huron, Michigan. In Michigan, it is a state trunkline highway that enters the state south of Coldwater and passes through the cities of Lansing and Flint. A north–south route from the Indiana–Michigan border to Lansing, it changes direction to east–west and continues to Port Huron and the US–Canadian border. In Flint, I-69 is also known as the Chevrolet-Buick Freeway, as a tribute to the Flint automotive industry. A 30-mile (48 km) stretch of I-69 between Flint and Perry is designated as the Pearl Harbor Memorial Highway. Until 2002, US 27 was concurrent with I-69 from the Indiana–Michigan state line north to the Lansing area.

I-69 in Michigan begins at the Indiana state line just south of Kinderhook. This is just north of an interchange with the Indiana Toll Road, which carries I-80 and I-90. From there, I-69 runs northward, passing through Coldwater and then Marshall, where it encounters I-94 for the first of two times. Near Olivet, I-69 begins to turn in a northeasterly direction, passing through Charlotte on its way into the Lansing–East Lansing metropolitan area.

On Lansing's west side, I-69 is concurrent with I-96, the only such palindromic pairing in the entire Interstate Highway System. Upon leaving the I-96 multiplex, I-69 changes cardinal orientation and is signed as east–west from that point on northwest side of Lansing through Flint to Port Huron. There, I-69 joins I-94 before both routes cross the Blue Water Bridges over the St. Clair River at the Canadian border, their common eastern termini and the only jointly named Interstate freeway to make a Canadian border crossing.[citation needed] I-69 is also at present the only mainline Interstate Highway in the state of Michigan that does not enter the Metro Detroit area, as well as being one of only two odd-numbered mainline Interstate Highways in America to be signed east-west (along with I-75 in South Florida).

The earliest freeway portion of I-69 in Michigan is a stretch built in three stages from 1959 to 1961 running from near Perry to Swartz Creek as the M-78 freeway. In 1962, the stretch of I-96, which now overlaps with I-69, was built west of Lansing. Another stretch of current I-69 alignment was built in 1964 as part of I-94 in the Port Huron area which ended at the foot of the Blue Water Bridge. In 1966, another stretch was built as M-21 near Port Huron which connected with I-94. The portion bisecting Branch County, Michigan was built in 1967. The M-78 freeway was extended eastward passing through Flint and ending at Lapeer in 1971. The M-78 portion of the extended freeway ended in Flint and the stretch of the freeway from the Genesee–Shiawassee county line to Lapeer was designated M-21. The original stretch of I-69 between Fort Wayne, Indiana, and Lansing was concurrently designated as US 27 until that route was truncated to Fort Wayne in 2002.

Temporary I-69 between Charlotte and Morrice was a divided highway originally designated as part of M-78. I-69 also replaced part of M-21 east of Flint. In 1984, two portions of I-69 alignment were completed, a stretch from I-96 to US-27 northwest of Lansing (designated US-27 at first) and the portion between Lapeer and Port Huron which was designated I-69 upon its completion. The final 12-mile (19 km) stretch of I-69 between Charlotte and I-96 was opened in October 1992. It completed Michigan's original state-wide Interstate Highway System, although plans for a northern stretch of I-275 outside Detroit were abandoned because of local opposition.

The Lansing-to-Port Huron segment shortened travel time between those two cities, allowing motorists to bypass Detroit along the way, in which I-69 is the only mainline Interstate in Michigan to not go through the city of Detroit, or even Metro Detroit. The northeastern portion of I-69 in Michigan provides a more direct route from Chicago to Toronto, east of the junction with I-94 near Marshall.