The Irish got within a touchdown in the third quarter, but Thompson broke loose from a tackle in the backfield for a 33-yard touchdown on a fourth-down play in the fourth quarter.
McGuinness again tried to rally, but Lewis fumbled on the goal line with 2:14 remaining to seal the game.
Lewis finished with 236 yards on 27 carries and three touchdowns, but it was the fumbles that stand out.
Irish coach Justin Jones, though, doesn't necessarily believe that.
“I'm not going to say turnovers were a difference in that game,” he said. “Turnovers are a part of football. The difference in the game was about five plays.”
Thompson, meanwhile, finished with 153 yards on the ground and 102 through the air, while Woodberry finished with 106 yards and nine carries.
After the game, the Titans' attention was already turned to next week when they host No. 2 Guthrie in the annual rivalry game.
It'll conclude the toughest stretch of the regular season for the Titans, too. It's also the stretch they failed to win a game in last season.
“We're about to get through with Murderer's Row and I'm ready to get through,” Rose said. “I hope we can survive the last step.”