But a failed fourth-down conversion by the Vols led to a Missouri field goal and sent Tennessee to a 51-48 defeat in Neyland Stadium.
Andrew Baggett’s 35-yard field goal was the difference.
Missouri, in its first trip to Neyland Stadium, twice erased a 14-point deficit in the second half.
Tennessee led 21-7 at halftime after its defense, maligned for giving up a school-record 721 yards last week to Troy, surrendered just 64 yards in the first half.
Running back Kendial Lawrence began the second half with a 77-yard touchdown run, puling the Tigers within a touchdown and signaling an unfortunate reversal for UT’s defense.
In the final two quarters, UT saw its lead fall away as it surrendered 303 yards of offense to the Tigers.
Lawrence again scored on a 1-yard touchdown run to make the score 28-21 with 4:12 remaining in the third quarter.
Tennessee (4-6, 0-6 SEC) clung to that seven-point lead as Missouri (5-5, 2-5) embarked on an 11-play drive on its final possession in regulation.
Tigers quarterback James Franklin twice completed passes on fourth down, first connecting with Marcus Lucas for a 17-yard gain to the UT 23-yard line.
The next one was even tougher to take.
Facing fourth-and-12 from the UT 25 with less than a minute remaining, Franklin was able to buy time in the pocket before finding Dorial Green-Beckham in the end zone with 47 seconds to go. Baggett’s extra point tied the game at 28-28.
Tennessee got good field position after the Tigers kicked off short, but after failing to gain a yard on two plays the Vols let time run out and opted to send the game to overtime.
In the first overtime period, Jimmie Hunt — whose 87-yard kickoff return touchdown was the Tigers’ only score in the first half — scored on Mizzou’s second play.
The Vols answered, with Bray finding Rajion Neal for an 8-yard touchdown and tying the game at 35-35.
In the second overtime, Tennessee lined up for a field goal at the 5-yard line, but holder Tyler Drummer ran a called fake in for the score and a 42-35 lead.
Missouri answered three plays later on third down, when Franklin connected with Marcus Lucas to tie the game and force another extra period.
Both teams scored in the third overtime, but neither was able to convert the mandatory two-point try, sending the Vols to a fourth overtime for the first time since their 2007 win at Kentucky that clinched its last SEC East title.
This time, though, Tennessee’s day didn’t end with a celebration.
Tyler Bray, who finished with more than 400 yards passing for the third time this season, completed a 7-yard pass to Marlin Lane on first down. His next three passes fell incomplete, including one in the end zone intended for Justin Hunter.
Missouri took over and ran the ball twice for 8 yards before Franklin moved to set up Baggett’s game-winning field goal try.
The Vols must now win their final two remaining games — Saturday at Vanderbilt and Nov. 24 against Kentucky — to earn a bowl berth.
Saturday’s game against Vanderbilt will kick off at 7 p.m. (TV: ESPN2).