McLaren captured five wickets for 19 runs from 3.5 overs to earn the Man-of-the-Match award, as West Indies, chasing 137 for victory from their 20 overs, were dismissed for 123 with one ball to spare at the Vivian Richards Cricket Ground.
The 27-year-old McLaren finished with the second-best figures in a Twenty20 international behind Pakistans Umar Gul, who collected five for six from three overs against New Zealand at The Oval in London in last years World Twenty20.
Both the West Indies and South Africa came into Wednesdays match having failed to make it through to the knockout stages of this years World Twenty20, which England won in Barbados on Sunday.
Its a good way to start off the tour having practised indoors and not outdoors for the last few weeks, said McLaren.
But its only the first day, and theres plenty more cricket to come, so hopefully, I can better this performance.
We all know the nature of T20 cricket - the bowler is always up against it. You can take five wickets one day, and the next day, take a thumping, but I enjoyed it.
South Africa captain Graeme Smith added: It was not an easy day for the batters, and you had to graft pretty hard.
Playing shots was not easy, and there was a strong wind, so there were a lot of things you had to take into consideration.
It was obviously nice to start with a win. This was the most important thing for us.
We have worked really hard over the last few days here in Antigua, had a few discussions, the energy has been good around the team, and a lot of new faces have come in.
We want to have a good tour of the Caribbean, so success in this match was very important to getting us off on the right foot.
Earlier veteran South African batsman Jacques Kallis had struck one four and three sixes in 53 from 45 balls, as South Africa laboured to 136 for seven from their 20 overs, after deciding to bat on an uneven pitch.
He added 73 for the second wicket with Smith, whose 37 from 31 balls included three fours and one six.
Once they were separated, South Africas batting collapsed, and they lost their last five wickets for 16 runs from 26 balls.
McLaren then became only the fourth bowler to collect five wickets in a T20 match, when he ripped out Andre Fletcher caught behind by stand-in keeper AB de Villiers for a duck, and had the dangerous West Indies captain Chris Gayle caught at long-on for 14 to leave the hosts on 28 for two in the sixth over.
Johan Botha snuffed out a West Indies revival, when he had Dwayne Bravo caught at long-on for 20 in the 10th over, and Narsingh Deonarine stumped by de Villiers for a duck two balls later.
When Roelof van der Merwe had Ramnaresh Sarwan caught at cover off the leading edge in the 11th over, West Indies still needed 85 from 56 balls, and there was little or no substance nor stability from the rest of the batting.
It was a disappointing start for us, said Gayle. We wanted to put our dismal performance in the T20 World Cup behind us, but this was not the best way to do it, and was not the best start to the series.
We still have a match on Thursday, so we have to pick ourselves up. This is no time for pointing fingers.
We have a lot of corrections to make out there, and we have to return to the drawing board to try and get the best out of the players.
G. Smith st Fletcher b Miller 37
L. Bosman c Fletcher b Taylor 7
J. Kallis c Sarwan b Pollard 53
A. de Villiers c Taylor b Pollard 11
J. Duminy b Roach 0
J. Botha c Fletcher b Roach 0
A. Petersen run out (Fletcher) 6
R. McLaren not out 6
R. van der Merwe not out 4
EXTRAS: (lb3, w4, nb5) 12
TOTAL: (7 wkts) 136
Did not bat: D. Steyn, C. Langeveldt
Fall of wickets: 1-15; 2-88; 3-111; 4-115; 5-115; 6-122; 7-127
Roach 4-0-25-2 (nb5, w1)
Bravo 1-0-14-0 (w1)
Pollard 4-0-22-2 (w2)
C. Gayle c Smith b McLaren 14
Fletcher c de Villiers b McLaren 0
D. Bravo c (sub) Amla b Botha 20
Sarwan c Petersen b van der Merwe 13
Deonarine st de Villiers b Botha 0
K. Pollard b McLaren 27
D. Sammy st de Villiers b McLaren 17
Miller c de Villiers b Langeveldt 5
Taylor run out (de Villiers/Steyn) 7
S. Benn c Amla b McLaren 4
K. Roach not out 3
EXTRAS: (lb1, w11, nb1) 13
TOTAL: (all out) 123
Fall of wickets: 1-14; 2-28; 3-48; 4-50; 5-52; 6-88; 7-99; 8-111; 9-120
van der Merwe 3-0-17-1 (w1)
Steyn 4-0-23-0 (nb1, w7)
McLaren 3.5-0-19-5 (w2);
Botha 4-0-19-2 (w1)