After Australia posted 294 for nine in their innings, South Africa reached their victory target with more than 13 overs remaining.
The 23-year-old De Kock hit 11 sixes and 16 fours in 113 balls to record the second highest ODI score by a South African batsman after Gary Kirsten hit 188 against the United Arab Emirates at the 1996 World Cup in Pakistan.
De Kock flayed the visiting bowlers to all corners in the high altitude batting paradise of the Highveld.
He featured in an opening stand of 145 before Rilee Rossouw was trapped lbw for 63 to the first ball from leg spinner Adam Zampa.
He then put on another 123 runs with captain Faf du Plessis and was the fourth wicket to fall, caught on the boundary by Travis Head off Scott Boland.
Australia had begun their innings brightly with David Warner (40) and Aaron Finch (33) making good starts while George Bailey top scored with 74 off 90 balls.
South Africa, however, took regular wickets and kept the run rate under six on the Centurion pitch, which traditionally favours the team batting second. Andile Phehlukwayo, playing only his second ODI for South Africa, took 4-44. The teams meet next at the Wanderers in Johannesburg on Sunday.
(Reporting by Mark Gleeson; Editing by Toby Davis)
