The margin of victory, which gave the hosts a 3-0 series sweep, is second only to New Zealand's 290-run thrashing of Ireland in 2008.
It is the biggest one-day win by South Africa and the heaviest defeat for Zimbabwe, topping the Proteas's 212-run triumph over their neighbours in Centurion last year.
Duminy smashed a career-best 129 from 117 deliveries and De Villiers hit 109 in 99 balls, his second successive hundred, as the home team amassed 399 for six in 50 overs.
The pair's 219-run partnership was a South African record for the third wicket.
Zimbabwe were then skittled out for 127, seamer Juan Theron claiming three for 18.
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