Roy made 87 and Stokes an ODI-best 75 as England, bidding for a first 5-0 clean sweep of a home one-day series, set Pakistan a challenging total to chase.
At 244 for five England -- who posted a world record 444 for three in the third ODI in Nottingham -- were set for another huge score. But Pakistan pegged them back with paceman Hasan Ali taking an ODI best four for 60 and left-arm quick Mohammad Amir three for 50.
England made a rapid start after being sent into bat on a green-tinged pitch and under overcast skies by Pakistan captain Azhar Ali, who clearly hoped his pace bowlers could exploit the helpful conditions.
Alex Hales struck Amir, recalled in place of the injured Mohammad Irfan, for three successive fours in as many balls at the start of the fifth over.
The lively Hasan then dismissed Joe Root for a mere nine when the batsman inside-edged an attempted drive on to his stumps. England were 92 for three after Imad Wasim, born in the nearby south Wales city of Swansea, struck with his third ball when England captain Eoin Morgan (10) tamely chipped a full toss straight back to the left-arm spinner.
Wasim finished with fine figures of one for 33 in his maximum 10 overs. Roy, who has been in excellent ODI form for England this season, averaging over 62, with two hundreds against Sri Lanka, twice launched off-spinner Malik for straight sixes.
Left-handed batsman Stokes struck seamer Umar Gul and spinner Mohammad Nawaz for two straight sixes before suffering a painful blow when he inside-edged an attempted pull off Gul into his groin.
After several minutes' treatment, Stokes batted on before he flicked Hasan to Gul at short fine leg. England were in danger of falling short of 300 until Chris Jordan launched Gul for six in the last over.
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