Knox County is a county located in the U.S. state of Tennessee. As of the 2020 census, the population was 478,971, making it the third-most populous county in Tennessee. Its county seat is Knoxville, which is the third-most populous city in Tennessee. Knox County is included in the Knoxville metropolitan area. The county is located at the geographica…Knox County is a county located in the U.S. state of Tennessee. As of the 2020 census, the population was 478,971, making it the third-most populous county in Tennessee. Its county seat is Knoxville, which is the third-most populous city in Tennessee. Knox County is included in the Knoxville metropolitan area. The county is located at the geographical center of the Great Valley of East Tennessee. Near the heart of the county is the origin of the Tennessee River, at the confluence of the Holston and French Broad rivers.