Luck, who has been the Colts' starter since 2012 as a rookie from Stanford when he replaced Peyton Manning, was on the sideline for a preseason game Saturday night in Indianapolis against the Chicago Bears when ESPN reported the news.
Luck -- already ruled out of the game due to an ankle injury -- had met with Colts owner Jim Irsay earlier to tell him of the decision.
After the game, he publicly confirmed his decision during a 25-minutes news conference though he said an official announcement was planned on Sunday.
"I've been stuck in this process," an emotional Luck told reporters. "I haven't been able to live the life I want to live. It's taken the joy out of this game ... the only way forward for me is to remove myself from football.
"This is not an easy decision. It's the hardest decision of my life. But it is the right decision for me.''
Some Colts fans booed him as he walked off the field after the 27-17 loss to the Bears.
"I'd be lying if I said I didn't hear it," Luck said of the boos. "Yeah, it hurt."
During his first three seasons in the NFL, Luck led the Colts to the playoffs, including back-to-back AFC South titles and the AFC Championship Game in 2014. Last season, the Colts made the playoffs -- beating the Houston Texans but losing to the Kansas City Chiefs.
"We have nothing but gratitude and thankfulness for the blood, sweat and tears he spilled as No. 12," Irsay said. "Part of our heart is broken tonight. We know we must go forward."
Luck has been beset with injuries, including this year when he sustained a calf strain that kept him out of the team's offseason activities and minicamp. Luck took part in only three days of training camp with limited participation.
"I'm in pain; I'm still in pain," he said. "It's been four years of this pain, rehab cycle. It's a myriad of issues -- calf strain, posterior ankle impingement, high ankle sprain. Part of my journey going forward will be figuring out how to feel better.''
Two week ago, he said he first started thinking about retirement.
General manager Chris Ballard said they started discussing the potential decision early last week.
"It was Monday," Ballard said. "We all sat down and had a talk and continued through the week. Emotional talks on our parts. Not any negative emotional talks. Just some real honest talks. But did not get a sense. I watched Andrew go through the shoulder, his routine and how he rehabbed and worked through things. He was going through the same process all the way from when he walked in the building. He came in Monday and started working through this."
He has missed 26 games -- including the entire 2017 season -- with shoulder, kidney and rib injuries.
But in 2018, he threw for 4,593 yards and 39 touchdowns to win NFL Comeback Player of the Year and lead the Colts back to the playoffs for the first time since the 2014 season.
In Week 3 of the 2015 season, he also had a shoulder injury.
Luck, who turns 30 on Sept. 12 -- four days after the season opener at San Diego -- finishes his career with 2,000 completions, 3,290 attempts, 23,671 yards, 171 touchdowns and 83 interceptions.
ESPN.com's Adam Schefter reported that Luck won't have to pay $12.8 million bonus money from the two years left on his five-year contract in 2016 for $140 million as allowed under the collective bargaining agreement. His five-year extension included a $32 million signing bonus that was prorated out to a cap hit of $6.4 million per year.
In addition, the Colts could have sought Luck's 2019 roster bonus of $12 million paid out in March, according to agent Joel Corry.
That year, Brissett started 15 games, throwing for 3,098 yards, with 13 touchdowns and seven interceptions. The Colts were 4-11 record in Brissett's 15 starts, and he ranked 27th out of 30 qualified quarterbacks.
Caesars Sportsbook moved Indianapolis' Super Bowl odds from 12-1 to 30-1 after Luck's announcement.