Word first leaked about Luck's plans during the fourth quarter of Saturday's 27-17 loss to the Chicago Bears when ESPN's Adam Schefter first reported Luck felt mentally worn down and had met with team owner Jim Irsay to inform him of his decision.
Luck has most recently struggled to recover from a lower left leg injury.
Luck's former coach Chuck Pagano made his first return to Lucas Oil Stadium since he was fired as the Colts' head coach following the 2017 season. Luck did not play that season because he was recovering from surgery on his throwing shoulder.
He returned last season and led the Colts back to the playoffs for the first time in four years, winning the league's Comeback Player of the Year award.
But in March, he suffered a strained left calf, was held out of all of the team's offseason workouts and returned on a limited basis for three practices at training camp in July. Lingering pain forced him back to the sideline and the Colts later determined that he had an injury near the back of his left ankle.
Coach Frank Reich had said he hoped to have an answer about Luck's availability for the Sept. 8 season opener after the third preseason game. This might not have been the one he wanted — and certainly didn't expect.