The left-hander plundered 10 sixes and seven boundaries in the first-ever international century in the shortest format of the game to lift the West Indies to 205-6 after being given first strike.
A sell-out crowd of 32,000 at the Wanderers were at hand to see the home team attempt the daunting target of 10.3 runs an over to win the first match of the 12-nation tournament.
Devon Smith contributed 35 in an opening stand of 145 with Gayle, the highest in Twenty20 cricket surpassing the 132 by South African captain Graeme Smith and Loots Bosman against Pakistan earlier this year at the same venue.
Gayle, who limped through the latter part of his innings due to a leg sprain, finally fell in the 17th over when he top-edged a pull off Johan van der Wath.
The West Indies, who were 178-2 at one stage, lost four wickets in the last four overs to help the South Africans contain the runs in the end.
Gayle did not look back after cutting the first ball of the tournament from Shaun Pollock for a boundary and then pulled the veteran for a six in his second over.
There was no respite for Makhaya Ntini bowling from the other end as Gayle lofted him for two successive sixes and the West Indies raced to 42-0 in the first four overs.
The left-hander pounded the Morkel brothers, cutting Morne for a six to third man that bounced off Pollock's hands and then smashing Albie out of the stadium at mid-wicket.
When South African captain Graeme Smith came to bowl off-spin in the 12th over, Gayle charged out to smack him over long-on for his seventh six.
Two more sixes came off successive balls in the next over off Pollock who finished his quota of four overs conceding 52 runs for the wicket of Marlon Samuels.
West Indies 206/6 in 20 overs (Gayle 117, Devon Smith 35; van der Wath 2 for 33, Philander 2 for 35) Vs South Africa.