De Villiers scored 115 from 102 balls with ten boundaries and three sixes -- his 15th one-day hundred -- to lift South Africa to an imperious 268-7 before bowling Pakistan out for 151 in 35.3 overs.
Sohaib Maqsood top-scored with a solid 53 but otherwise Pakistan failed to capitalise on a weakened South African bowling attack, with spearheads Dale Steyn and Morne Morkel, and spinner Imran Tahir rested for the meaningless match as the series had already been decided.
"It is satisfying to win the series and I think the players played exceptionally well throughout the series and played as a unit," said De Villiers.
"It was tough to bat on this pitch but I hung on and we were thinking of 220-plus, but in the end we got a good total."
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Pakistan captain Misbah-ul Haq rued another batting failure.
"I think they played very well," said Misbah. "They deserved this win and it was the same old batting collapse. We have to seriously think about this."
It was Maqsood, who hit 56 on his debut in Abu Dhabi on Friday, who gave some consolation to another lackluster batting effort with a 63-ball half-century before he became one of two victims for Jean-Paul Duminy, who finished with 2-14. Wayne Parnell finished with 3-36.
Umar Akmal made 30 while Misbah managed 18. Shahid Afridi (nine) and Umar Amin (five) failed once more as South Africa took the last six wickets for a mere 41 runs.
De Villiers lifted the tempo in the final overs, hitting Sohail Tanvir's final over for 25 runs, reaching his hundred with a four towards mid-wicket, which came off 99 balls.