The New York Giants will line up with a quarterback other than Eli Manning for the first time since 2004 on Sunday after coach Ben McAdoo chose to name Geno Smith as the man to face the Oakland Raiders.
Manning has started 210 consecutive regular-season games, as well as 12 in the playoffs - the longest active streak in the NFL and second only to Brett Favre's all-time record of 287.
Speaking after the decision was announced, the 36-year-old Manning said he was unhappy about it but had no option but to keep pushing.
"It's hard," Manning said in comments reported on the Giants website. "It's been a hard day to handle this. But hang in there and figure it out."
With the Giants struggling at 2-9 and much attention on their ageing quarterback - a two-time Super Bowl winner but now fading - McAdoo said he had discussed the idea of starting Manning before introducing ex-New York Jets quarterback Smith in the second half.
But Manning said he did not want to start a game he would not be allowed to finish.
"I just didn't think that you start knowing that you're going to come out of a game to keep a streak alive," Manning said. "That's not what it's about. It's not a pre-season game, where you're going to play the start to the half, what's the next week?
"A quarter, a series, that's not fair. That's not fair to me, that's not fair to Geno, that's not how you play. You play to win. You're named the starting quarterback, you think it's your job to go win the football game."
McAdoo, who was on the Green Bay coaching staff during Favre's streak, said he respected Manning's decision.
"The streak obviously is very important to Eli," McAdoo said. "I have a lot of respect for everything that Eli has done in this league and for this organisation, and a lot of respect for the streak.
"I see what he goes through each and every week to get ready to play and how consistent he is. I don't want to speak for Eli, but I don't believe he would want to tarnish the record, and I'll leave it at that."
But he insisted this was not the end of Manning's tenure in New York.
"I have a lot of confidence in Eli as a player, as a quarterback," McAdoo said. "But at this point, it's my responsibility for the organisation to make sure we take a look at Geno and at some point take a look at Davis (Webb), and give them the opportunity to show what they can do heading into next year."
Earlier this season, Eli overtook his elder brother Peyton's record of 208 consecutive starts, set between 1998 and 2011.
After Manning sits, the Los Angeles Chargers' Philip Rivers is in line to take over as the player with the longest active streak. The 35-year-old, who was traded to the Chargers for Manning after the 2004 draft, has started 187 straight regular-season games.