Pietersen hit 111 not out off 98 balls, the first time he had passed fifty on England's tour of the UAE, as Alastair Cook's side turned the tables on Pakistan who had beaten the tourists 3-0 in the Test series.
Cook fell 20 short of scoring his third consecutive one-day international century but put on 170 with Pietersen for the first wicket, the best opening stand for England against Pakistan.
A target of 223 was never in doubt despite Cook falling caught behind to Saeed Ajmal. Eoin Morgan helped Pietersen make his first three-figure score since his knock against India in November 2008, and closed out the match with 76 balls to spare.
Steven Finn and Stuart Broad did the damage with the ball as they both took three wickets after their fine early bursts had reduced Pakistan to 50-4.
But a composed 50 from Umar Akmal and an entertaining 51 from Shahid Afridi briefly threatened to restore Pakistan's confidence until Broad and James Anderson removed the threat.
Finn had claimed four wickets in the first two ODI games and Pakistan's batsmen had trouble playing him again.
The Middlesex quick had Imran Farhat caught behind by wicketkeeper Craig Kieswetter for nine while at the other end Broad also looked dangerous.
Azhar Ali was out to Broad as Kieswetter claimed another catch. Broad should have picked up Mohammad Hafeez's wicket too but the opener was reprieved on 17 when Broad's delivery was deemed a no-ball despite Morgan claiming a catch at point.
But Finn trapped Hafeez leg before for an entertaining 29 and Pakistan were reeling when captain Misbah-Ul-Haq edged to Graeme Swann at slip to give Broad a second wicket.
Umar Akmal and Asad Shafiq fought hard for a 47-run partnership before the latter failed to properly ground his bat and was run out by Cook.
Umar Akmal steadily made his way to a 92-ball fifty while the explosive Afridi hit only his second half-century against England, which included a massive six off Swann.
But Broad ended the pair's 119-run partnership by claiming a third wicket thanks to an excellent catch by Samit Patel at midwicket as Umar Akmal produced a leading edge. Afridi was to follow shortly afterward as Anderson knocked over his leg stump as the Pakistan batsman went for another big hit to add to his 51 runs off 55 balls.
Finn took his third wicket bowling Adnan Akmal, Anderson also knocked over Saaed Ajmal and last man Aizaz Cheema was run out on the last ball as Pakistan added just 42 in their last nine overs.
In response, Cook and Pietersen raced toward the target taking 60 off their first 10 overs. That included 15 runs off Umar Gul's third over after the bowler produced three no balls.
The pair were rarely troubled until Cook was eventually dismissed although Pietersen had a letoff while on 45 as he found Azhar Ali at deep midwicket off Cheema. However, the Pakistan batsman could not hold on to the resultant straightforward catch.