The 28-year-old Jamaican shattered the top order during his incisive eight-over spell by dismissing Shahid Afridi (one), Imran Farhat (13). He then claimed Faisal Iqbal (30) when he returned for his second spell.
Powell's 3-33 restricted Pakistan to the modest total after the home side elected to bat here on Wednesday.
Powell bowled Afridi off his fourth ball and then had Farhat caught in the slip in his sixth over to put the depleted home team under pressure from the outset.
Fellow paceman Dwayne Smith then dismissed Mohammad Hafeez (one) and Shoab Malik (nought) to leave Pakistan struggling at 47-4 in 17 overs.
Yasir Hameed, who made 71, led the recovery through a 62-run fifth wicket stand with Iqbal.
The 28-year-old Hameed, playing his first match in 12 months, hit three boundaries in his snail-paced 118-ball knock.
Abdul Razzaq (33) added 45 quick runs for the eight wicket with Rana Naved-ul-Hasan (18) to boost the total.
The home team was without captain Inzamam-ul-Haq who was ruled out due to finger injury. Also missing was key batsman Mohammad Yousuf who skipped the match to attend his pregnant wife.
Paceman Umar Gul and spinner Abdul Rehman were rested to make way for Afridi, Mohammad Sami, Hameed and Iqbal.
West Indies were boosted by the return of middle-order batsman Shivnarine Chanderpaul who had been suffering from knee injury. Also included were Powell and Mohammed. The tourists rested Corey Collymore (flu), Daren Ganga and Jerome Taylor.
Pakistan lead the five-match series 2-0 after winning the second match at Faisalabad by two wickets and the third in Lahore by seven wickets. The first match was washed out.