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.
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.
Business interests, however, guided largely by Knoxville's trade connections with cotton-growing centers to the south, contributed to the development of a strong pro-secession movement within the city. Thus, while East Tennessee and greater Knox County voted decisively against secession in 1861, the city of Knoxville favored secession by a 2-1 margin.