Rizwan and Irfan both suffered hamstring injuries in the third match in Rawalpindi, where a second-string New Zealand side won by seven wickets to level the five-match series 1-1
Mohammad Rizwan (78) and Haider Ali (68) put on a dominant batting performance as Pakistan set the tourists a target of 201 in Karachi.
The bowlers finished the job for the home team after Mohammad Wasim picked up four wickets and Shadab Khan took three as West Indies were skittled out for 137.
Pakistan's 18th T20 win in 2021 was an improvement on their record of 17 victories in 2018.
The second and third matches in the series will be played on Tuesday and Thursday respectively.
The teams are scheduled to play three one-day internationals after the T20 series.