AB 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 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 was already decided.
Pakistan were 8-2 with Ahmed Shehzad (two) and Mohammad Hafeez (six) by the fifth over, once again highlighting the top-order failure in the series.
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 skipper Misbah-ul Haq 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.
The South African skipper hit a 102-ball 115 studded with ten boundaries and three sixes to lift South Africa who won the toss and batted on a slow Sharjah stadium pitch.
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. He then hit the left-armer for six, four and four to help South Africa add 114 in the last ten overs.
At 105 he also completed 6,000 one-day runs, becoming the fifth South African batsmen to reach the milestone. Jacques Kallis (11,469), Herschelle Gibbs (8094), Graeme Smith (6976) and Gary Kirsten (6798) were others to score 6,000 or more one-day runs for South Africa.
De Villiers was initially slow, reaching his fifty off 70 balls, with a big six off Saeed Ajmal towards mid-wicket. He added an invaluable 83 for the sixth wicket with Ryan McLaren (27) before lashing out in the final overs.
De Villiers had built the innings with an invaluable 62 runs stand for the fourth wicket with Faf du Plessis who made an 89-balls 46 with the help of two boundaries.
Quinton de Kock (34) added 50 with Du Plessis after Hashim Amla fell in the first over of the innings for three. Ajmal finished with 3-45 while Khan took 2-57.
South Africa won the first match by one run in Sharjah before Pakistan levelled the series with 66-run win in Dubai. South Africa then won both the matches in Abu Dhabi by 68 and 28 runs respectively.
The two teams now play Twenty20 internationals in Dubai on Wednesday and Friday.