Manistee is a city in the U.S. state of Michigan. Located in southwestern Manistee County, it is part of the northwestern Lower Peninsula. Manistee is the county seat of Manistee County, and its population was 6,259 at the 2020 census. This makes Manistee the fifth-largest city in Northern Michigan. Manistee is located on an isthmus between Manistee Lake and Lake Michigan, with the Manistee River bisecting the city as it flows west to the latter.