Down by three, the Colts were in Patriots territory, threatening to repeat last year's dramatic 35-34 victory over New England and pull off a comeback win as time was running out.
But Sanders assured there would be no repeat, nabbing New England's third interception to ice the game.
Tom Brady went 19-of-25 passing for 186 yards and two touchdowns, winning his 25th straight regular season home game as a starter for the Patriots (8-2), who stayed tied with the New York Jets for the AFC East lead.
Manning threw for 396 yards and four touchdowns, completing 38 of his 52 pass attempts in the setback, which put the Colts (6-4) into a tie with Jacksonville atop the AFC South.
Swim Week Miami Beach 2014 [PHOTOS]