Duminy scored 64 in 89 balls while Du Plessis made 55 from 60 after South Africa won the toss and batted at Sheikh Zayed Stadium.
For Pakistan Mohammad Irfan took three wickets while Shahid Afridi and Saeed Ajmal took two wickets apiece.
The five-match series is tied at 1-1 after South Africa won the first match by one run in Sharjah while Pakistan won the second in Dubai by 66 runs.