Chasing a challenging 267-run target, Pakistan were bowled out for 238 in 49.2 overs with Dale Steyn taking a career best 5-25.
Misbah-ul Haq top-scored with 65 while debutant Sohaib Maqsood made 56.
For South Africa, opener Quniton de Kock hit a maiden hundred with 112 while Hashim Amla(46) and AB de Villiers (30) were other contributors.
The fifth and final match is in Sharjah on Monday.
AFP