Hashim Amla's unbeaten score of 122 led the way as South Africa saw off Zimbabwe by 93 runs to win the first one-day international in Bulawayo.
Hosts Zimbabwe won the toss and chose to field, but could only take three wickets as South Africa reached 309-3 from their 50 overs.
In reply, both Hamilton Masakadza (61) and Sean Williams (51) notched half-centuries, but they were the only men to make a serious dent on the scoreboard as the tourists bowled them out for 216 with one ball to spare.
Both Aaron Phangiso and Imran Tahir claimed three wickets each for the Proteas.
South Africa can seal the series by winning the second of three ODIs on Tuesday, also in Bulawayo.