The Proteas' top order largely failed to fire but De Villiers ensured his side reached 268 for seven.
Totals of 259 and 266 were enough to win the two previous games in Abu Dhabi by 68 and 28 runs respectively and Pakistan, the designated "home" team, were again unable to rise to the challenge.
They were bowled out for 151 with almost 15 overs wasted, Wayne Parnell taking three for 36 to set up a thumping 117-run win despite 53 from Sohaib Maqsood.
Mohammad Irfan trapped Hashim Amla lbw in the first over but South Africa reached 45 for one in the first 10 overs, Quinton de Kock with 31 of those from 33 balls.
The left-hander added only one more, though, before going back to a Saeed Ajmal delivery and becoming another lbw casualty.
JP Duminy made just two before hitting Mohammad Hafeez straight to silly mid-on but Faf du Plessis and De Villiers rebuilt with a patient stand of 62.
Du Plessis fell four short of a hard-won half-century when he heaved Junaid Khan straight to deep square leg and David Miller's poor series concluded with a painstaking 15.
De Villiers brought up his fifty with a six off Ajmal and repeated the feat four overs later, while Ryan McLaren consistently found the boundary in a brisk 27 as the pair put on 83.
Back-to-back fours had taken De Villiers into the 90s and after hitting the third ball of the final over to the rope to reach a 99-ball century, he added a six and two more fours to round off the innings in style.
Hafeez hit the second ball of the Pakistani response for four but they were soon in trouble, starting when Ahmed Shehzad hooked Lonwabo Tsotsobe straight to long leg Vernon Philander.
Philander bowled Hafeez in the next over and when Umar Amin fell lbw to the same bowler, it was 17 for three.
Captain Misbah-ul-Haq lofted Tsotsobe down the ground for six but made only 18 before pulling Ryan McLaren straight to mid-on.
Maqsood's half-century featured seven boundaries, a mixture of ferocity and finesse, and his stand of 54 with Umar Akmal was the highest of the innings.
But when the latter was dismissed for 30, plumb lbw in JP Duminy's first over after a forlorn review, the rot set in again.
Shahid Afridi skied a return catch to Parnell, Maqsood lofted Duminy to long-on, Parnell quickly removed Ajmal and Irfan and Sohail Tanvir edged McLaren to wicketkeeper De Kock to end the game.
The two sides will meet again later this month for two Twenty20 internationals and three ODIs in South Africa.
- Sports & Recreation
- De Villiers
- Saeed Ajmal
- Wayne Parnell
- Mohammad Irfan
- Mohammad Hafeez