De Villiers was in typical free-scoring form, hitting six fours in his 88-ball knock to put the Proteas in sight of a big score after winning the toss on a flat MCG wicket.
But after de Villiers departed in the 43rd over with the score at 230 for five, the South Africans only mustered another 37 runs in the remaining seven overs.
De Villiers looked set for his 19th ODI century before paceman Pat Cummins lured him into a hurried shot with a slower, wider delivery which he top-edged and was caught by Steve Smith.
With him went the South Africans’ momentum as bowlers Cummins, Mitchell Starc and James Faulkner strangled their scoring and restricted the Proteas’ total.
David Miller was next best with 45 off 61 balls with three boundaries, before he fell to Faulkner, and Faf du Plessis made 28 from 37 balls.
Cummins finished with two for 61 off 10 overs and medium-pacer Faulkner, bowling slower balls out of the back of his hand, grabbed two for 45.
South Africa must win the match as they trail Australia 2-1 in the five-match series ahead of Sunday’s final game in Sydney.