And just like his previous 11 seasons in Indianapolis, he had it down.
Wayne made one of his trademark moves to outmanoeuvre a Houston defensive back with 19 seconds left, freeing himself for a one-yard touchdown catch that gave the Colts a stunning 19-16 victory over AFC South champion Houston.
The five-time Pro Bowler celebrated by flinging his hands into the air, pointing toward the fans he loves and hugging his teammates before heading to the Colts' locker-room for possibly the final time.
"I said if this is going to be the last game, I want to go out with a bang. It was great," Wayne said. "It was a great feeling to go out. Hopefully, I'll be back but you never know."
Wayne, whose contract is up after the season, certainly made a strong case to return with the Colts in 2012.
The five-time Pro Bowler finished with eight catches for 106 yards, the biggest, of course, giving Indianapolis (2-13) a second win in five days. It was Wayne's third 100-yard day of the season and put the Colts' No. 2 all-time receiver in position to match another franchise record with eight straight 1,000-yard seasons.
Indy's suddenly strong finish could jeopardize the Colts' stronghold on the No. 1 overall draft pick, having tied the league's other two-win teams -- St. Louis and Minnesota.
But Wayne and his teammates could care less about that chase. They wanted a win, and some of them wanted to win for teammates such as Wayne, Robert Mathis and Jeff Saturday, who were cornerstones of one of the league's model franchises. All of them have expiring contracts.
"I was kind of in my hotel room thinking today and kind of know it's the last home game of the season here and there's question marks about what can happen in this future, and I was thinking if it ever got to the point in the game where somebody needed to make a play, it wasn't probably going to go anywhere but (Wayne)," quarterback Dan Orlovsky said. "I think he deserved that opportunity."
Orlovsky finished 23 of 41 for 244 yards with the one touchdown and won his second straight after losing his first nine NFL starts. Even sweeter, he beat the team he played for the past two seasons.
For Houston, it was a bitter reminder that they hadn't completely swung the balance of power in the AFC South.
Having already clinched the franchise's first playoff berth and still playing for a first-round bye, the Texans (10-5) seemed poised for a playoff tuneup in Indianapolis.
Instead, they looked anything but playoff-ready.
Houston settled for two field goals in the red zone, didn't convert a third down until getting a lucky bounce late in the fourth quarter, its running game was stymied late and the defence helped the Colts with three penalties on the decisive drive.
"The last two were absolutely unnecessary on my part," rookie defensive end J.J. Watt said after being called for two of the penalties. "That's on me. I can't do that. I can't hurt our football team like that."
Houston is now 0-10 in Indianapolis and hasn't scored more than 20 points in a game since T.J. Yates took over as the starting quarterback.
Yates was solid, 13 of 16 for 132 yards with a rating of 101.0, and Arian Foster had a big day rushing 23 times for 158 yards.
But when the Texans had to sustain drives or punch it into the end zone, they squandered away scoring chances.
"We make one play offensively at the end, the game's over," coach Gary Kubiak said. "We make one stop at the end, the game's over."
At the start, the game certainly looked as if it would be a repeat of the Texans' 34-7 season-opening blowout when Brian Cushing beat the Colts blockers on the game's first play, sacking Orlovsky and stripping the ball. Foster ran for eight yards on the next play, then scored on a nine-yard burst off the left side to give Houston a 7-0 lead.
The teams traded five field goals over the next 58 minutes, but the Colts never had the lead.
Then somehow Orlovsky got rolling. He connected with Pierre Garcon for 11 yards and Jacob Tamme for 10. After a three-yard completion to Donald Brown, Wayne caught a 34-yard pass on third-and-7 to keep the drive alive with 51 seconds left. Houston's three penalties moved the ball to the Houston one-yard line, and on first-and-goal, Orlovsky lobbed the pass to Wayne, who hauled it in for the momentous catch.
"It's big," Wayne said. "For one thing, not knowing what my future's going to be, just wanting to get a win, couldn't get anything better than this."
NOTES: Before the game, Colts owner Jim Irsay told NFL Network that if Peyton Manning plays next year, it will be in Indianapolis. ... Wayne also moved past Rod Smith for No. 18 on the NFL's career receptions list. Smith finished with 849. Wayne now has 854. ... Houston's four-game winning streak came to an end. ... Adam Vinatieri missed a 42-yard field goal just before halftime, ending his streak of 33 consecutive field goals made at Lucas Oil Stadium.