Swashbuckling openers Mitch Marsh and Travis Head led the charge on Friday, before allrounder Cooper Connolly and Ollie Peak also chipped in with the bat at Harare Sports Club.
Australia made two changes to the side that won Tuesday's opening game at the same venue by 59 runs, recalling Josh Hazlewood and Billy Stanlake for fellow quicks Xavier Bartlett and Spencer Johnson.
Zimbabwe went with the same XI.
Stand-in Aussie captain Marsh, who lost the toss and was sent in to bat, was dropped at backward point off Blessing Muzarabani's first ball of the game by Wesley Madhevere.
Head showed his intention early, whipping off his pads the first six of the contest in just the third over.
Marsh's first maximum came the following over and he survived an lbw shout off Brad Evans' bowling as the tourists raced to 78 off 10 overs - which included nine fours and four sixes.
The spin of Sikanda Raza was introduced in the 12th over, in which Head reached his 18th ODI half-century, off 32 balls, and Marsh brought up his 21st off 52 deliveries with another six.
Marsh was dismissed 11 balls later, bowled for 53 by a peach from left-arm spinner Wellington Masakadza (2-51), and Australia were 1-130 after 19 overs.
Head was joined at the crease by Connolly, who watched the 32-year-old South Australian bring up his eighth ODI century off just 75 balls.
But after Head went soon after for 112 - the highest one-day score by an Aussie against Zimbabwe - the tourists lost Josh Inglis (21) and Alex Carey (20) to be 4-286 with 6.4 overs remaining in the innings.
Connolly (78) recorded his third ODI half-century, before game-one hundred-maker Matt Renshaw was out for 15 chasing quick runs. Ollie Peake finished 41 not out from just 18 balls in Australia's total of 6-356.
Evans was the pick of the home side's bowlers, taking 3-86.
The three-match series is part of defending champion Australia's preparations for next year's World Cup in southern Africa.
Australia have rested regular skipper Pat Cummins for the three ODIs, before he joins the team in South Africa for three one-dayers and next month's three Tests.