Dealing with a nerve issue in his elbow that is causing tingling in his fingers, Mariota missed one game and failed to pass for more than 103 yards in two others before breaking out last weekend against the reigning Super Bowl champions.
Mariota threw for two touchdowns and rushed for another score to rally the Titans to a last-second 26-23 victory over the Philadelphia Eagles in overtime last week.
Tennessee (3-1) will take a three-game winning streak into Sunday's matchup at the reeling Buffalo Bills (1-3), who have scored the fewest points in the AFC (50) and are coming off a 22-0 drubbing at the Green Bay Packers.
Each of the Titans' three victories has come by three points, but it was the manner in which they took down Philadelphia that was most impressive. Tennessee trailed by 14 points in the third quarter before Mariota ignited the comeback.
With Mariota making a sparse contribution due to his elbow/hand issue and even sitting out Week 2, the Titans failed to crack 20 points in the first three games. Mariota guided Tennessee to 23 points after halftime against Philadelphia, punctuating his performance by connecting with wide receiver Corey Davis for a game-winning 10-yard touchdown pass with five seconds left in the overtime session.
The late heroics earned Mariota AFC Offensive Player of the Week honors. He finished 30 of 43 for 344 yards with the two TDs and an interception. He added 46 yards rushing on 10 carries.
"Honestly, it's really a credit to the guys," said Mariota of the weekly award. "Without every single one of those guys on offense, that would not have been possible. It's cool to have a team recognition, and hopefully we can get a few more of those."
The Bills opened the season with a pair of lopsided losses before springing a 27-6 upset win at the Minnesota Vikings in Week 3. However, they turned in a dreadful performance at Green Bay, managing 145 yards of total offense and leaving head coach Sean McDermott grasping for positives.
"As we go and develop these guys ... you go through this and say, 'Hey, we're a young team, and there's going to be some of these moments,'" said McDermott. "As hard as it is, you gotta understand where we are in this building. And these moments, if you learn from these scars that we're taking on, if you're using it the right way, you'll look back and say, 'That was good for us.'
"We get the right education early and the guys learn from it. And those teams, those individuals that stick with it usually come out on the right end of it at the end of the process."
That process has been painful for both the team and rookie quarterback Josh Allen, the No. 10 overall pick in this year's draft who will make his third start Sunday. Buffalo ranks dead last in passing yards, percentage of interceptions and sacks allowed per attempt.
The running game has been non-existent -- partially due to the fact that the Bills have spent so much time playing from behind. LeSean McCoy has been held to 85 yards in the three games he has played on just 21 carries. Allen leads the team with 116 yards rushing.
"It's tough," said McCoy, who rushed for over 1,000 yards last season for the sixth time in his career. "The only thing I can control is making things happen when the ball is in my hands."
Defensively, the Bills haven't been awful. They're ranked ninth in yards allowed per play, 11th against the rush and 15th overall. But given how much the offense has struggled, the burden on the defense is magnified.
"I don't know that burden is the right name for it," said defensive tackle Kyle Williams. "But I think that we feel like we need to be better. I think we felt like as far as limiting points or doing some things on Sunday, we were OK. But we can tighten some things down and be even better. We feel like we can be a good defense, we feel like we should to help our offense."
Tennessee also will be trying to get its running game going. Derrick Henry has 163 yards rushing through four games and is averaging only 3.0 yards per carry. Henry had just eight carries for 24 yards Sunday against the Eagles.
Backfield mate Dion Lewis had 30 carries in the first two games, but that number dwindled to 13 in the past two contests. Lewis was held to zero yards on four attempts against the Eagles.