East Tennessee was Union country inside a Confederate state, and everyone knew it. When Ambrose Burnside's Army of the Ohio marched into the region in late August 1863, the occupation of Knoxville on September 1 was nearly bloodless. Pro-Union citizens welcomed Federal troops with open arms. But the strategic picture shifted violently after the Confederate victory at Chickamauga on September 19-20. Braxton Bragg, looking to rid himself of a subordinate he found troublesome, ordered James Longstreet to detach his corps and recapture Knoxville. Longstreet wanted 20,000 men. Bragg gave him 10,000 infantry, 5,000 cavalry, and 35 guns, along with broken-down locomotives and maps so inaccurate that they placed the French Broad River in the wrong location. The campaign was hobbled before it began.

On November 17, as Burnside's men raced to fortify Knoxville, Brigadier General William P. Sanders and 600 dismounted cavalrymen stood between the city and Longstreet's advancing divisions. Sanders posted his troopers on a bare hilltop west of Third Creek, behind a breastwork of fence rails. The 8th Michigan Cavalry carried Spencer repeating rifles, and two cedar trees marked the center of a line that was all that stood between the Confederates and an unfinished defense network. Sanders held through fog, artillery, and three infantry assaults. When Confederate snipers occupied the upper story of a nearby home called Bleak House, a Union artillerist fired a 20-pounder Parrott rifle at extreme range and burst a shell inside the room. Captain Orlando Poe, Burnside's chief engineer, called it the prettiest shot he saw during the entire war. By late afternoon on November 18, the Confederates finally overwhelmed Sanders' line. Sanders himself fell, fatally wounded, likely by one of the Bleak House snipers. He died the next morning, having been a brigadier general for exactly one month. The fort he helped save was renamed Fort Sanders in his honor.

Longstreet's 15,000 men simply could not surround a city defended by roughly 12,000 Union soldiers backed by the Tennessee River. Technically, it was never a true siege. Pro-Union farmers in the French Broad River valley east of Knoxville smuggled in 10,000 bushels of corn, 6,000 bushels of wheat, 1,500 hogs, 1,000 cattle, and more. Longstreet's faulty map showed the French Broad in the wrong place. When pro-Confederate civilians tried to correct the error, the general doubted their loyalty and ignored them. Meanwhile, Captain Poe orchestrated one of the most resourceful defensive efforts of the war. Old telegraph wire was strung between tree stumps in front of Fort Sanders, creating one of the earliest wire entanglements in military history. The Union garrison built a ring of forts and batteries across the ridges north and south of the river, each eventually named for Union officers killed during the campaign.

At 6:20 on the freezing morning of November 29, after a 20-minute artillery bombardment, roughly 2,400 Confederates charged Fort Sanders. The front ranks stumbled into the wire entanglement, fell, rose, and surged forward. Then they reached the ditch. The parapet towered above a deep trench with slippery clay walls angled at 70 degrees. Longstreet's binocular observation had been fatally wrong. Men clawed at frozen mud while defenders poured fire from above. Lieutenant Samuel Benjamin lit the fuses on artillery shells and hurled them by hand into the ditch among the packed Confederates. The assault collapsed within minutes. The Confederates suffered 813 casualties, including 129 killed. Union losses inside the fort numbered roughly 20. Half an hour after the assault failed, Longstreet received word that Grant had crushed Bragg at Missionary Ridge four days earlier. Some Union defenders from the IX Corps considered the victory personal revenge for their humiliation at Fredericksburg a year before.

Longstreet held on for five more days, hoping to draw Sherman's relief force away from Bragg's shattered army. When Sherman approached with 30,000 men, marching without artillery to move faster, Longstreet withdrew northeast on the evening of December 4. The retreat was miserable. Rain turned to freezing cold, and barefoot soldiers left bloody tracks on the frozen roads. By December 9, the Confederates reached Rogersville, leaving behind the wounded, the sick, and stragglers who were captured. Sherman arrived at Knoxville on December 6 and was irritated to find Burnside's garrison in reasonable condition, not the starving force he had been led to expect. Burnside's men were still wearing their tattered summer uniforms, but they were alive and unbroken. The entire siege cost the Federals 693 casualties against 1,296 Confederate losses. Longstreet lingered in East Tennessee until April 1864, launching inconclusive raids before finally being recalled to rejoin Lee in Virginia. A Confederate veteran later summed up the miserable campaign: 'All the boys used to say that all East Tennessee lacked of being hell was a roof over it.'