Hours after Pagano was sent home from the hospital, Luck became the first Colts quarterback to run for two touchdowns in a game since 1988 as Indianapolis put away the Cleveland Browns 17-13.
Interim coach Bruce Arians intimated he could almost hear Pagano cheering.
"He was at the house, and we're really excited about that," Arians said of Pagano, who is undergoing treatment for leukemia. "That's probably as big as the win today. ... I'm sure he's feeling great right now."
The victory came in typical Pagano style.
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Indy (3-3) controlled the ball for more than 35 minutes, ran for a season-high 148 yards, held Cleveland to 55 yards on the ground, and finished with two stops in Colts territory before finally forcing the last man with the ball out of bounds on the final play.
The Colts have one more win than they had all of last season, and the biggest reason has been Luck -- who won this season's first head-to-head matchup among the five rookie starting quarterbacks.
Luck didn't follow the traditional script.
While he had a solid day throwing the ball, finishing 16 of 29 for 186 yards with no touchdowns or interceptions, he was more efficient running it. He had three carries for 12 yards, becoming the third quarterback in franchise history with two rushing TDs in a game. Ricky Turner did it on Dec. 4, 1988, against Miami, and Bert Jones accomplished the feat on Oct. 20, 1974, against the Jets.
For the first time all season, Luck didn't have to rally the Colts at the end.
But it was team owner Jim Irsay's postgame speech about Pagano that made Luck feel even better.
"I'm thrilled to hear that. I'm more thrilled about that than the win," Luck said.
The Browns (1-6) took the field on Sunday with heavy hearts after team officials said Friday that left guard Jason Pinkston had been hospitalized due to life-threatening blood clots.
Brandon Weeden did everything he could to rally his teammates, going 25 of 41 for 264 yards, two touchdowns and no interceptions. He just didn't get enough help.
After Greg Little made a beautiful juggling catch in the back of the end zone for a 14-yard TD, punter Reggie Hodges dropped the ball on the extra point, putting the Browns in a 7-6 hole that they couldn't overcome.
The defense couldn't seem to stop the Colts at critical times.
Running back Trent Richardson attempted to play despite a rib injury, but after managing eight yards on eight carries in the first half, he was yanked by coach Pat Shurmur and didn't return in the second half.
"The injury was pretty bad, I guess it limited me a lot," Richardson said. "I sat down, so, you know, it just hurt me not being out there, hurt me inside not being out there.
"I didn't want to come out. I said Pat knows what's best. He made his decision, and I think he made a great decision."
Without a healthy Richardson, the Browns' ground game got stuck.
Weeden still had chances to rally the Browns after Luck opened the game with a 3-yard TD run and a 5-yard TD dash on the Colts' first two possessions.
Then, with 7:25 left in the game, Sheldon Brown recovered Luck's fumble at the 50. Three plays later, Weeden threw a perfect 41-yard strike to Gordon in the end zone. But instead of taking the lead, Gordon dropped the ball. Cleveland punted on the next play to the dismay of Browns fans and new owner Jimmy Haslam.
"He makes that catch nine times out of 10, so be it, it didn't happen on this day, but I stay positive with him," Weeden said. "He's made a lot of big plays. He's coming into his own and he's becoming a really good player."
The defense answered with another stop, and Weeden marched the Browns to the Colts 39 -- a drive that ended when a fourth-and-6 pass to Josh Cooper fell incomplete.
Cleveland got the ball back one more time, needing to go 80 yards in 1 second. All the Browns could do was run a play with five laterals and a fumble before Josh Cribbs was finally shoved out of bounds -- setting off the celebration at Pagano's home.
"Hopefully, he [Pagano] didn't get too dag gone exhausted coaching from the bedroom, and his count didn't go down," Arians said. "As long as his count stays up, he'll be OK."
- Browns defensive tackle Ahtyba Rubin left with a calf injury during the first half and didn't return. Brown hurt his left ankle and left briefly.
- Cleveland has lost 11 straight road games. The Browns haven't won two in a row against the Colts since 1988.
- Reggie Wayne caught six passes for 73 yards, and rookie Vick Ballard ran 20 times for 84 yards for the Colts.
- Colts right tackle Winston Justice left in the second half with an ankle injury.