Madison County is located in the north central portion of the U.S. state of Alabama. As of the 2020 Census, the population was 388,153, making it the second-most populous county in Alabama. Its county seat is Huntsville. Since the mid-20th century it has become an area of defense and space research and industry.

Huntsville is the most populous city in the U.S. state of Alabama. It is the county seat of Madison County with portions extending into Limestone County and Morgan County. It is located in the Appalachian region of northern Alabama.