Huntsville is the most populous city in the U.S. state of Alabama and 95th most populous in the US. It is the county seat of Madison County wit…Huntsville is the most populous city in the U.S. state of Alabama and 95th most populous in the US. 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 south of the state of Tennessee.