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The Colts selected Manning first overall in the 1998 NFL draft and served as their starting quarterback from 1998 to 2010. He helped transform the struggling Colts franchise into consistent playoff contenders, leading them to 11 playoff appearances, eight division titles, three AFC Championship Games, two Super Bowl appearances, and one championship title in Super Bowl XLI, the franchise's first in over three decades and first since relocating to Indianapolis. Manning was also named Super Bowl MVP in the victory. After undergoing neck surgery that sidelined him for the 2011 season, Manning was released by the Colts and signed with the Broncos. Serving as the Broncos starting quarterback from 2012 to 2015, he helped them clinch their division each season and reach two Super Bowls. Manning's career ended with a victory in Super Bowl 50, making him the first starting quarterback to win the Super Bowl for more than one franchise.

Manning holds many NFL records, including most MVP awards,[16] quarterback first-team All-Pro selections, 4,000-yard passing seasons, single-season passing yards, and single-season passing touchdowns. He is also third in career passing yards and career passing touchdowns. Helping lead both the Colts and Broncos to two Super Bowls each, Manning is the only quarterback to have reached the Super Bowl with multiple franchises and multiple starts for each. He was inducted into the College Football Hall of Fame in 2017 and the Pro Football Hall of Fame in 2021.