India claimed a 2-1 series triumph after posting 5-176 on Saturday night at Adelaide Oval - the highest women's T20 international score at the venue.
Australia mustered 9-159 in reply, losing traction after their initial three wickets - including Ellyse Perry in her 350th international match - fell in a 13-ball span.
Australian openers Georgia Voll and Beth Mooney cracked 18 runs from the first over, delivered by Renuka Singh Thakur.
But Voll (10) and Mooney (six) were dismissed in a space of six balls.
Australian great Perry scored only one - she advanced to spinner Shreyanka Patil and attempted a big drive but missed and was bowled.
Perry's dismissal left the hosts reeling at 3-32 in the fourth over and Phoebe Litchfield and Ash Gardner steadied with a 31-run stand.
But Litchfield (26 from 17 balls) was caught in the deep from consecutive switch-hits - she smacked a four from the first one - to leave the hosts 4-63 in the ninth over.
The Australians were 4-78 at the midpoint and Gardner gave her side a sniff, making 57 from 45 balls before she too was caught in the deep.
Gardner's departure started another Australian slump of 4-15.
Earlier, Indian opener Smriti Mandhana top-scored with a superb 82 from 55 balls and featured in a 120-run partnership with No.3 Jemimah Rodrigues (59 from 46).
Australia struck early when quick Kim Garth (1-25) dismissed Shafali Verma (seven) in the third over.
Mandhana and Rodrigues then produced their fine stand, powering the tourists to 1-86 at the midpoint of their innings.
The 29-year-old Mandhana registered her half-century from only 38 balls by smacking Darcie Brown over the midwicket fence for six.
The partnership was finally broken in the 17th over when Mandhana lofted Annabel Sutherland (2-34) into the legside only for Gardner to make swift ground from deep midwicket and take a catch on the run.
Rodrigues posted her half-century from 41 balls as Richa Ghosh added late impetus with 18 from seven balls.
The nations meet again on Tuesday in Brisbane for the first of three 50-over fixtures, ahead of a Test match starting March 6 at the WACA Ground in Perth.
The trophy at the end of the multi-format series is decided on a points system, with two points for a T20 and 50-over victory and four points on offer for a Test triumph.
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