Du Plessis has found himself under the spotlight in the United Arab Emirates due to a lack of form and the controversy of the the second Test when he was found guilty of ball tampering.
While that did not result in a ban for the right-hander - who used the zipper on his whites to change the condition of the ball - his position in South Africa's line-up has grown doubtful after managing just 51 runs at an average of 12.7 since landing in the Gulf.
But Du Plessis (55) more than doubled his tour aggregate, after being promoted to three, as he reached a half-century for the first time in 12 ODI innings. With top-scorer JP Duminy also adding 64 they provided the basis of 259 for eight after batting first.
It was a total that proved beyond Pakistan as they were bowled out for 191 from 44.3 overs following a middle-order collapse inspired by leg-spinner Imran Tahir (four for 53).
Tahir claimed three wickets in a collapse that paved the way for South Africa to take a 2-1 lead in the five-match series.
After Dale Steyn ended a 50-run opening stand when he had Ahmed Shehzad caught by fellow returnee Hashim Amla at slip, Pakistan were still handily-placed at 86 for two before their collapse set in.
The rot began in the 20th over when the third umpire sent Umar Amin back for a referred edge behind off Lonwabo Tsotsobe.
Tahir then got to work in the next over as skipper Misbah-ul-Haq took too long to review an lbw decision that appeared to hit his thigh. Asad Shafiq and Umar Akmal then both fell to soft dismissals, the latter chipping a full toss back to Tahir, and when Shahid Afridi was lbw to Ryan McLaren Pakistan were 116 for seven.
Wahab Riaz (33) and Sohail Tanvir (31) combined in a 59-run stand to add some respectability but they were left with too much to do.
McLaren ended the match when Tanvir guided a short ball to Amla at midwicket.
Amla had missed the opening two matches after awaiting the birth of his second child but managed just 10 to prompt Du Plessis' earlier-than-expected walk to the crease.
Du Plessis was promoted in a new-look top-four after Graeme Smith was ruled out for the rest of the series due to post-concussion syndrome after being hit on the temple during the second Test.
Du Plessis shared a 77-run stand with Quinton de Kock (40) before reaching his long-awaited half-century with back-to-back boundaries off Riaz and from 54 balls.
The 29-year-old was out next over though, like De Kock stumped off Afridi, and their quickfire exits could have destabilised the innings.
Duminy ensured that was not the case as he piloted consecutive half-century stands with AB de Villiers (34) and David Miller (34) while reaching his own 50 from 67 balls.
The left-hander finally departed in the penultimate over, picking out midwicket off Tanvir, but in a low-scoring series the required spade work with the bat had already been done.