Former two-division champion suffers second career setback in a fight-of-the-year contender in Manchester, England.
The pair engaged in one of the contenders for fight of the year at Manchester Arena.
Warrington, an underdog with the bookmakers despite relieving Lee Selby of the world title in May, was rewarded for a huge workrate to earn his 28th win from 28 fights.
The judges gave it to Warrington 116-112, 116-112, and 116-113 in his first title defense.
Frampton came back into the fight in the middle rounds but couldn't sustain the pressure and lost for only the second time in 28 bouts, and a second world title fight.
- Carl Frampton