Buttler's 52-ball 116 not out -- his hundred coming off just 46 deliveries -- coupled with a maiden century by opener Jason Roy lifted England to an imposing 355-5 before Pakistan were bowled out for 271 in 40.4 overs.
The win gave England their second series win since the World Cup disaster earlier this year where they failed to qualify for the quarter-finals.
They also beat New Zealand 3-2 at home but lost to Australia by the same margin.
Pakistan needed to improve upon their best-ever run chase -- 327 against Bangladesh in March last year -- but despite good knocks from Babar Azam (51 off 51 balls), Shoaib Malik (34-ball 52) and skipper Azhar Ali (44 off 32 balls) they fell short.
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Mohammad Hafeez made 37 and Anwar Ali 24 as spinners Moeen Ali (3-53), Adil Rashid (3-78) and seamer David Willey (2-34) took wickets at regular intervals to stop Pakistan from pulling out a series-levelling win.
It was Buttler who stole the limelight ahead of Roy.
Buttler smashed medium-pacer Anwar for his eighth six to complete his third one-day century off just 46 balls -- also the joint-seventh fastest one-day hundred -- to help England score 129 in the final ten overs.
He improved his own record of a 61-ball hundred -- the previous fastest hundred for England -- made against Sri Lanka at Lord's in May last year.
Buttler's batting heroics overshadowed Roy's 117-ball knock after England, who won the toss and batted, thrived on a batsman-friendly pitch.
Roy added 140 for the second wicket with Joe Root (71) to set an ideal platform for Buttler.
Roy took a single off leg-spinner Yasir Shah to complete his three figures off 113 balls but two runs later was caught off the same bowler.
Roy, whose previous best of 67 came against Australia at Southampton in September, hit eight boundaries and a six.