Brandon King made a sparkling 72 but the rest of the West Indian innings failed to fire in the third ODI against the Proteas in Potchefstroom on Tuesday.
The West Indies were bowled out for 260 after they were sent in by Aiden Markram, captaining South Africa in the absence of Temba Bavuma, who had a hamstring strain.
Opener King struck 11 fours and a six in a 72-ball innings studded with elegant drives.
But the rest of the West Indian batting failed, apart from innings of 39 by Nicholas Pooran and 36 by Jason Holder.
There were no significant partnerships after King and Shamarh Brooks (18) put on 71 for the second wicket to take the West Indies to 110-2 after 19 overs.
Brooks was run out when he slipped in mid-pitch and King followed 10 runs later when he played the ball onto his stumps in trying to guide Lungi Ngidi to third man.
The West Indies lead the series 1-0 after the first match was rained off.
© Agence France-Presse