Powell, who spearheaded the attack in place of Jerome Taylor and Corey Collymore, snared a trio of top order batsmen to finish with three for 33 as Pakistan were bowled out in 49.5 overs
Leading the five-match series 2-0 after the first match in Rawalpindi was washed out, Pakistan were missing the services of three leading batsmen, captain Inzamam-ul-Haq, Mohammad Yousuf and Younis Khan.
Inzamam is nursing a finger injury while the other two senior players had personal matters to attend to.
Yasir Hameed capped his return to international cricket after nearly a year out with a fluent 71 as Pakistan, led by Abdul Razzaq, floundered on a pitch that encouraged the bowlers.
Hameed picked up the innings with a fifth wicket stand of 62 from 97 balls with Faisal Iqbal (30) after Pakistan had slipped to 47-4.
Later on in the innings, Razzaq (33) and Rana Naved (18 from 13 balls) put on 45 from 34 balls for the eighth wicket to give some respectability to the total.
Powell spoiled explosive all-rounder Shahid Afridi's return to the team by bowling him in the second over for one and then had Imran Farhat caught by Chris Gayle at gully for 13 in his first spell of eight overs.
Dwayne Smith, who took two for 29, made it 45-3 when he had Mohammad Hafeez (1) caught iat slip by Gayle before trapping Shoaib Malik leg before for a duck.
Hameed and Iqbal lifted the total to 109 with some smart cricket before Powell returned to have the latter caught in the deep by spinner Dave Mohammed.
Hameed, who made his 11th fifty in his 49th match, was dismissed in the 41st over with the total on 141, caught by Powell at deep mid-wicket as he tried to blast a Mohammed delivery out of the ground.
Kamran Akmal and Naved were run out and Razzaq was caught at long on as Pakistan added 70 runs in the final 10 overs.
Fast bowler Mohammad Sami was handed his first start of the series as Pakistan made four changes, while experienced batsman Shivnarine Chanderpaul returned for the West Indies after missing the first three games.
Pakistan 209 all out in 49.5 overs (Yasir Hameed 71, Faisal Iqbal 30, Abdul Razzaq 33; Darren Powell 3 for 33, Dwayne Smith 2 for 29, Ian Bradshaw 1 for 43) Vs West Indies