The hosts, after winning the toss and batting first, made an imposing 207-7 from their 20 overs on a much-improved Sabina Park pitch.
Stand-in Captain Brandon King, who stood out with a top score of 79 in the first T20I, got the ball rolling quickly on Saturday with a 13-run third over off the bowling of Anrich Nortje, who South Africa brought in for this game in place of Gerald Coetzee.
Johnson Charles, playing his 50th T20I, once again failed to make any inroads with the bat as he was first to fall, caught in the deep off the bowling of Bjorn Fortuin for seven.
Kyle Mayers joined the skipper and the pair brought the score up to 51-1 at the end of the first powerplay with King 35* off 20 balls and looking set for another big one and Mayers on nine from seven balls.
Unfortunately for the hosts and the Sabina Park crowd, King’s knock didn’t last much longer as he became the first T20I wicket for debutant Nqaba Peter when he was caught at long on for 36 in the seventh over.
Peter got his second wicket not long after when Mayers, after hitting a six the ball before, became the third West Indies batsman to get out caught in the deep. He made a 16-ball 32 including two fours and three sixes. The score at the time of his wicket was 83-3 with one ball left in the ninth over.
At the halfway point, the hosts were 88-3 with Roston Chase and Andre Fletcher at the crease on 10 and three, respectively.
The pair then batted beautifully to put on a further 56 in short time before Fletcher fell for 29 to leave the West Indies 139-4 with five overs left.
Not long after, Chase brought up an excellent maiden T20I fifty with a flat six over mid-wicket off Lungi Ngidi in the 17th over. His milestone came off 30 balls.
The 19th over proved to be the most crucial for the West Indies as a trio of sixes from Romario Shepherd brought the score past the 200 mark before he fell off the last ball of that over for 26 off just 13 balls.
In the end, Chase finished 67* off just 38 balls including seven fours and two sixes.
Peter was the pick of the South African bowlers with 2-32 from his four overs while Ngidi and Andile Phehlukwayo took 2-41 and 2-51 from their respective four over spells.
The start from South Africa then had Sabina Park silent as openers Reeza Hendricks and Quinton De Kock absolutely hammered the West Indian bowling around the park on the way to an opening partnership of 81 in the first five overs.
The last ball of that fifth over proved to be the start of the West Indian fightback as De Kock took one risk too many and was bowled by Akeal Hosein for 41 off just 17 balls including four fours and as many sixes.
Three balls later, one became two for the Windies as Reeza Hendricks, who made 87 in the first game on Thursday, was dismissed by Chase for 34 to leave the tourists 83-2 at the halfway point of the sixth over.
Ryan Rickelton and Matthew Breetzke then added a further 30 before the latter went for an ill-advised second run and was run out thanks to a brilliant throw from the deep mid-wicket boundary by Shamar Joseph for 12 off the penultimate ball of the 10th over.
Rickelton was next to go, caught off the bowling of Romario Shepherd for 19 to leave the score at 124-4 off 12 overs.
Not long after, Andile Phehlukwayo fell to another brilliant piece of fielding from Joseph, this time a catch in the deep off the bowling of Gudakesh Motie for three to leave the South Africans reeling at 138-5 in the 15th over.
Any chance South Africa had of pulling off the chase was dashed when Gudakesh Motie dismissed both Rassie Van Der Dussen (30) and Wiaan Mulder (9) in the 17th over.
In the end, South Africa reached 191-7 from their 20 overs, 16 runs short of their target.
Motie ended with 3-22 from his four overs while Shepherd bowled a crucial spell with 1-21 from his four.
Chase, who was named man of the match, completed a fine all-round performance with 1-26 from his four overs.
Chase says the team has eyes on a series sweep.
“Obviously we’ve started the series well being 2-0 up but three is better than two. I just think it’s for us to look at some of the areas where we were weak today and plan to execute them better tomorrow and improve on the areas we did well in as well,” he said.
“The guys have been playing some good cricket, we just had a camp in Antigua and we’ve put in a lot of hard work so it’s just for us to come out and execute and mostly, enjoy the cricket. I think once you go out there to enjoy the cricket, it becomes a lot easier and takes a bit of pressure off of you so it’s just to go out there and have fun,” he added.
The third T20I is set for Sunday.