Mariota's two touchdown passes included a 22-yard go-ahead toss to Eric Decker 6:06 left in the fourth quarter.
Derrick Henry wasn't happy with his performance in the season-finale. The two-point conversion attempt failed - and almost brought disaster for the Titans when Mariota was sacked, but officials ruled he was down before the ball came loose.
The Titans then ran out the clock and the Chiefs' season once again came to a heartbreaking halt at home despite forcing two turnovers and not committing one themselves.
As multiple Kansas City defenders ran at him near the line of scrimmage, Mariota saw an open man in the end zone and threw the ball.
Henry started for the second consecutive game in place of DeMarco Murray, who is sidelined by a knee injury.
The second-team All-Pro caught a pass over the middle and was going to the ground when Cyprien tried to lay a shoulder into him.
The Bills' only hope of victory lies in their ability to disrupt Jacksonville's run game-a tall order, seeing as the Jaguars' rushers are second to none this season-and expose their weakest link: Blake Bortles. The Chiefs finished the drive with a touchdown. It wouldn't matter, however, as the Titans would get another first down to secure the 22-21 win.
The Chiefs took a commanding 21-3 lead into halftime, but they failed to score the rest of the game.
Alex Smith connected with tight end Travis Kelce for a 13-yard touchdown pass with 2:15 left in the first quarter. The defense forced a stop, and kicker Harrison Butker hit the right upright on a 48-yard field goal attempt. Kelce was wobbly getting up, and ruled out for the game with a concussion.
The team is led by rookie running back Kareem Hunt who led the league in rushing (1,327 yards). Eager to melt the clock, the Titans put the ball in Henry's gut.
The win was the organization's first playoff win since 2003. But the play was blown dead by the officials, so even though Justin Houston picked up the fumble, the Titans got a chance to kick a field goal.