Fellow wicketkeeper Beth Mooney also scored an unbeaten ton on Sunday as Australia amassed 7-409, their highest domestic score and only three short of the home side's overall record.
India made a quick start to their massive run chase - they would have needed to break their own record to win - but they lost key wickets early and were never seriously in the hunt.
The tourists were bowled out for 224 in 45.1 overs, giving Australia a 185-run win and an unbeatable lead in the multi-format series.
After India took out the T20s two games to one, the hosts won the three ODIs ahead of the series-ending Test next week in Perth.
"Just to finish the ODI leg the way we did, it makes me really proud," Healy said.
Healy's imperious 158 is the highest women's one-day score against India and the highest women's one-day international innings in Australia.
"What a ridiculous sport that we play, that it can kick you down so many times and then give you opportunities like it has today," she said.
"I've hated every milestone match, so today was just an opportunity to go out and enjoy it. It was one of the more enjoyable experiences I've had, so thanks to the cricket gods for that, it was a nice way to sign off in the yellow."
Mooney then scored her century with three balls left and reached 106no.
Healy also bowled two overs when the result was beyond doubt, but her gentle finger spin did not threaten the Indians and she remains without an international wicket.
"It didn't take much to get talked into (bowling) - I heard my name mentioned once and I said 'righto'," Healy joked.
The Indians formed a guard of honour for Healy's last ODI innings, with the opener retiring from all cricket after next week's Perth Test.
Healy started cramping in the 80s, but that only seemed to fire her up more. The 35-year-old great belted 27 fours and two sixes in her 98-ball masterclass.
It was her eighth one-day international ton, equalling Karen Rolton and behind only Meg Lanning's 15 as the most by an Australian.
She was bowled trying a trick shot off an innocuous full toss from Sneh Rana, just 12 runs shy of her highest one-day international score.
Georgia Voll continued her excellent form with 62 in a second-wicket stand of 104 with Healy.
Mooney then joined the pile-on in a 145-run partnership with her skipper.
No.9 Nicola Carey belted an unbeaten 34 from 15 balls after Australia lost three quick wickets to help Mooney finish off the innings and ensure they passed 400.
Mooney only needed 84 balls for her century, hitting 10 fours and a six.
Rana and Sree Charani took two wickets apiece.
India posted a record 5-341 to beat Australia in last October's World Cup semi-final.
But in-form opener Smriti Mandhana made a fourth-ball duck on Sunday night to immediately put India on the back foot.
Leg-spinner Alana King took 4-33 from 10 overs, including the crucial wicket of Indian captain Harmanpreet Kaur.
King trapped Kaur lbw with an excellent straight ball for 25, leaving India 5-115 and no chance of a miracle. Jemima Rodrigues made 42 at No.3 to lead the early challenge before she top-edged Ashleigh Gardner to debutant Lucy Hamilton at fine leg.
Hamilton opened the bowling with her left-arm pace. She "badged" Deepti Sharma on the helmet with a bouncer, but the No.6 was able to keep batting and made 29, while Rana top-scored with 44.
Earlier on Sunday, Cricket Australia announced that the women's tour of the West Indies this month will not feature a Test - only three T20s and three ODIs.
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