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Set a mammoth 362 runs for victory from 42-overs in a rain-reduced affair, the West Indies could only muster 230 all out in 37.4 overs.
With the win in the final ODI, the Proteas claimed a comprehensive 4-1 series victory.
Only Marlon Samuels was able to score 50 (one four, four sixes) in the West Indies chase of a total simply out of their reach.
Samuels fell as soon as he reached his milestone in his 47-ball stay at the crease, clean-bowled by Kyle Abbott.
Chris Gayle was out for a duck first ball of their innings, and though there were contributions from Narsingh Deonarine (43), Dwayne Smith (31) and Denesh Ramdin (40) it was not nearly enough.
Wayne Parnell was chief-destroyer for South Africa with the ball with figures of 4/42.
Missing the services of their frontline bowling attack with Dale Steyn and Morne Morkel being rested and Vernon Philander nursing a groin niggle, it was up to the Proteas to post a big total batting first, a job they carried out with aplomb.
Hashim Amla, Proteas stand-in ODI captain, and Rilee Rossouw put together a record third wicket partnership for South Africa to steer the hosts to 361 for five batting first
Their stand of 247 runs from 181 balls eclipsed Amla's own previous record he held with AB de Villiers of 238 against Pakistan at the Wanderers in March 2013.
The partnership came to and end when Rossouw was out for his highest ODI score of 132 from 98 balls, having struck nine fours and eight sixes.
Rossouw was caught by Jonathan Carter off the bowling of Andre Russell.
Amla was also dismissed by Russell, dragging the ball onto his stumps for 133 from 105 balls including 11 fours and six sixes. It was Amla's 19th century in ODIs.
The pair came together with South Africa in a spot of bother at 59 for two, and after a measured start they began to dismantle the West Indies attack during the latter overs.
Earlier Quinton de Kock (4), returning in his first game from an ankle injury, lasted just seven balls, as he miscued a pull shot off Jason Holder with the catch looping to Carter at point to leave South Africa six for one.
Faf du Plessis made 16 before he fell to the bowling of Russell, caught at fine leg by Sheldon Cottrell.
The match started two-and-a-half hours late due to rain, and eight overs in each innings were lost.
Teams:
South Africa: Hashim Amla (captain), Quinton de Kock (wk), Faf du Plessis, Rilee Rossouw, David Miller, JP Duminy, Farhaan Behardien, Wayne Parnell, Kyle Abbott, Marchant de Lange, Aaron Phangiso.
West Indies: Chris Gayle, Dwayne Smith, Narsingh Deonarine, Marlon Samuels, Denesh Ramdin (wk), Jonathan Carter, Andre Russell, Darren Sammy, Carlos Brathwaite, Jason Holder (captain), Sheldon Cottrell
