Manning, 39, steps away holding almost every passing record in team history and a pair of Super Bowl rings. His victories over the New England Patriots after the 2007 and '11 seasons are the most iconic moments from a legendary career. They will put him in the conversation for the Hall of Fame in five years, when he's eligible.
Manning is one of just five players in NFL history with at least two Super Bowl MVPs. He's in an elite club with Joe Montana, Bart Starr, Tom Brady and Terry Bradshaw.
"For 16 seasons, Eli Manning defined what it is to be a New York Giant both on and off the field," John Mara, the team's president and chief executive officer, said Wednesday in a statement announcing Manning's retirement. "Eli is our only two-time Super Bowl MVP and one of the very best players in our franchise's history. He represented our franchise as a consummate professional with dignity and accountability. It meant something to Eli to be the Giants quarterback, and it meant even more to us. We are beyond grateful for his contributions to our organization and look forward to celebrating his induction into the Giants Ring of Honor in the near future."
The Giants will hold a news conference at 11 a.m. ET Friday, when Manning will address the media.
His decision to call it a career comes after a season in which Manning spent most of his time as the backup to rookie Daniel Jones. Manning made it clear after the season that being a backup wasn't much fun and there wasn't an interest in returning in a similar role, even if Mara left the door open for it to happen. Mara has also said it was possible Manning could return to the organization in another role if he decided to retire.
The Giants turned to Jones after Week 2 this season, and Manning started just four games, the lowest total since his rookie season. He won his final start as a Giant against the Miami Dolphins on Dec. 15 and received a proper send-off as he jogged off the field and into the arms of his wife and four children at MetLife Stadium.
Riddick: I'd put Eli in the Hall of Fame
Louis Riddick applauds Eli Manning for handling his 2019 campaign with class and expects him to be in the Hall of Fame conversation.
Manning was set to become a free agent this offseason. He has made more than $250 million from his football contracts, the most in NFL history.
His father, Archie, had long said he never thought Eli would play for another team. He will not, despite taking a month after the conclusion of the season to make his final decision.
Manning was the No. 1 overall pick in the 2004 NFL draft by the San Diego Chargers. But he didn't want to play in San Diego and was quickly traded to the Giants. The Chargers ended up with Philip Rivers and the Pittsburgh Steelers landed Ben Roethlisberger in the legendary '04 QB class. Manning is the first of the three to call it a career.
"I learned very early that you evaluate quarterbacks on their ability to win championships, and to do it late in a game when the game is on the line, that they're able to take a team down the field and into the end zone to win a title," former Giants general manager Ernie Accorsi, who engineered the trade for Manning, said in the statement.
"The second thing is to know that over a period of years, he's always going to be there. Those kinds of quarterbacks always give you a chance to win, and for 16 years, he did that for this franchise. He won championships and he was always there giving us a chance to win. I don't know how you can ask more from a quarterback."
Manning is seventh in NFL history with 57,023 passing yards, 366 touchdown passes and 4,895 completions. He finished with a 117-117 record as a starter in the regular season.
And then there were those two magical playoff runs that led to the two Super Bowl victories and MVPs. Those are part of the indelible mark Manning left on the game. He was the architect of two of the biggest upsets in Super Bowl history.
Manning went 8-4 in his playoff career, with five of those wins coming on the road. When the Giants beat Brady and the Patriots in Super Bowl XLII, it ruined New England's chance at an undefeated season in 2007.
That Super Bowl run in his fourth season included classic victories on the road in Dallas and Green Bay. Temperatures in the NFC Championship Game win over the Packers were below zero and Manning threw for 251 yards with no turnovers in the contest.
Two weeks later, he threw the game-winning touchdown to Plaxico Burress with 35 seconds remaining in the Super Bowl against the Patriots.
"It was an honor and privilege to coach Eli, and to go through the wonderful and magnificent moments that he and his teammates provided for all of us in the world championship '07-'08 and '11-'12 seasons," former Giants coach Tom Coughlin said in the statement.
"The New York Giants, flagship franchise of the National Football League, have four world championships. You have four trophies sitting there. You have (Phil) Simms, you have (Jeff) Hostetler, and you have Eli for two. Eli Manning not only is the quarterback on those great teams, but he is the MVP of the Super Bowls. He's an incredible big- game performer. You talk about a guy that's great to coach, focused every day, took tremendous pride in preparing, practice, had a great sense of humor, was a cynic in the locker room. But the guys loved him and they loved him for it, and they played for him. The guys that had the opportunity to play with him know what it's like to be with a guy with as much talent, as much grit, as much determination."
Manning took a vicious beating while defeating the San Francisco 49ers in the NFC Championship Game after the 2011 season. He entered the "elite" conversation while throwing for 296 yards and a touchdown in Super Bowl XLVI against the Patriots.
Manning went 69-50 as the starter in his first eight seasons. It went downhill from there. The Giants went 48-67 with Manning as the starter over his final eight seasons.
But that won't put a stain on one of the most unique careers in history. An iron man, Manning never missed a game because of injury and started 210 consecutive games from 2004 to 2017. He was a four-time Pro Bowl selection but never an All-Pro. He was never seriously in the running for an MVP.
Yet he retires as the most accomplished quarterback in franchise history and with two incredible playoff runs during 16 memorable seasons.
ESPN's Dan Graziano contributed to this report.