Opener Gibbs (102) and De Villiers (103 not out) put on 137 from 151 balls for the third wicket after Graeme Smith (34) and Jacques Kallis (8) had fallen in the first 20 overs.
Both made their second successive one-day hundreds following centuries against Zimbabwe at Harare in August.
Gibbs' century was his 18th in his 214th match while De Villiers brought up his third ODI ton.
The opener was in flowing form as he stroked 11 fours and one six in his 128 balls knock while De Villiers was more brutal, smashing nine fours and three sixes in his 95-ball innings.
He reached three figures in the penultimate over with a six and four.
Gibbs was run out in the 43rd over after he played the ball down to square leg and was beaten by a fast throw by Imran Nazir when attempting to come back for a second run.
Kallis failed for the first time on the tour after his record breaking 421 runs in the test series.
He played a loose shot to be caught and bowled by Shahid Afridi, who was by far the best bowler for the home side.
Gibbs entertained a big crowd with some brave shots as he and Smith put on 85 after South Africa had opted to bat after winning the toss.
Missing leading paceman Mohammad Asif through injury, the hosts were not helped by a wayward spell from Rao Iftikhar.
Debutant left arm paceman Sohail Tanvir, 22, conceded just 21 runs in his first six overs and returned to trap Justin Kemp (1) leg before but was than smashed around by De Villiers and Mark Boucher (14), who fell to Iftikhar in the penultimate over.
Smith who hit five fours was run out in the 15th over, beaten by a good flat throw by Mohammad Hafeez at deep mid-wicket.
South Africa won the two-test series 1-0 and are favourites to complete their tour with victory in the five-match ODI series.