World Cup hosts England made light of a seemingly challenging target of 359, Jonny Bairstow top-scoring with 128 as they won with 31 balls to spare.
Earlier, Imam-ul-Haq made a career-best 151 in Pakistan's 358 for nine, with England paceman Chris Woakes taking four for 67.
Brief scores
Pakistan 358-9, 50 overs (Imam-ul-Haq 151, Asif Ali 52; C Woakes 4-67)
England 359-4, 44.5 overs (J Bairstow 128, J Roy 76)
Result: England won by six wickets
Series: England lead five-match series 2-0