Opener Quinton de Kock hit a first T20 century as South Africa scored 259-4 after being set an imposing target of 13 runs per over to win the match.
Johnson Charles had led the West Indies to 258-5, a new record T20 total at the Pretoria test venue, after they had been put into bat and amassed a formidable total.
The 34-year-old from St Lucia set a West Indies record for the quickest century, achieved off 39 balls, eight fewer than Chris Gayle’s previous best mark.
Charles scored 118 off 46 balls before being bowled by Marco Jansen, South Africa’s best bowler with 3-52.
He hit 11 sixes - half of the West Indies total for the innings - which equalled the record 22 in an innings set by Afghanistan’s against Ireland three years ago.
Charles was ably supported by Kyle Mayers (51) in a 135-run second-wicket partnership followed by an unbeaten 41 from Romario Shepherd.
South Africa began at blistering pace in reply and by scoring 150 without loss off the first 10 overs set another T20 record.
De Kock took 43 balls to reach his century but departed straight after to end a 152-run opening partnership with Reeza Hendricks, who made 68 off 28 balls.
The pair succeeded in reducing the required run rate, allowing captain Aiden Markram (38 not out) to steer his side home to a remarkable win with seven balls remaining.
The batter-friendly pitch delivered a total of 35 sixes and 46 fours in a run feast for an enthusiastic crowd, producing 517 runs for the highest aggregate in a T20 international.
South Africa tied the three-match T20 series with the final game at the Wanderers in Johannesburg on Tuesday.
West Indies won the first match by three wickets on Saturday.
