There is significant evidence that Hernando de Soto visited Bussell Island in 1540.
The first major recorded Euro-American presence in the Knoxville area was the Timberlake Expedition, which passed through the confluence of the Holston and French Broad into the Tennessee River in December 1761.
Henry Timberlake, who was en route to the Overhill settlements along the Little Tennessee River, recalled being pleasantly surprised by the deep waters of the Tennessee after having struggled down the relatively shallow Holston for several weeks. Congress ordered all illegal settlers out of the valley in 1785, but with little success.
By the 1780s, Euro-American settlers were already established in the Holston and French Broad valleys. As settlers continued to trickle into Cherokee lands, tensions between the settlers and the Cherokee rose steadily. Two lots were set aside for a church and graveyard (First Presbyterian Church, founded 1792). That school was eventually chartered as Blount College and it served as the starting point for the University of Tennessee, which uses Blount College's founding date of 1794, as its own.
In 1790, White's son-in-law, Charles Mc Clung—who had arrived from Pennsylvania the previous year—surveyed White's holdings between First Creek and Second Creek for the establishment of a town. Also in 1790, President George Washington appointed North Carolina surveyor William Blount governor of the newly created Territory South of the River Ohio.
This he accomplished almost immediately with the Treaty of Holston, which was negotiated and signed at White's Fort in 1791.
Local agricultural products—especially tobacco, corn, and whiskey—were traded for cotton, which was grown in the Deep South.However, the approach of stronger Union forces under Ambrose Burnside in the summer of 1863 forced Buckner to evacuate Knoxville before the earthworks were completed. Like the Confederates, he immediately began fortifying the city.The Union forces rebuilt Fort Loudon and erected 12 other forts and batteries flanked by entrenchments around the city.Blount originally wanted to place the territorial capital at the confluence of the Clinch River and Tennessee River (now Kingston), but when the Cherokee refused to cede this land, Blount chose White's Fort, which Mc Clung had surveyed the previous year.Blount named the new capital Knoxville after Revolutionary War general and Secretary of War Henry Knox, who at the time was Blount's immediate superior.The KMSA is, in turn, the central component of the Knoxville-Sevierville-La Follette Combined Statistical Area, which, in 2013, had a population of 1,096,961.