Starting on their overnight score of 267 for six, the Cheteshwar Pujara-led side crashed to 274 all out as pace spearhead Gurinder Sandhu (4-76) wiped the India A tail within the first half hour of the fourth and final day's morning session at the MA Chidambaram Stadium.
Sandhu turned on the heat after sending back overnight batsman Shreyas Gopal (0) without troubling the score and then picked up Varun Aaron (1) and dangerman Baba Aparajith (30) in his next couple of overs to flatten India A hopes.
Needing 61 for a win, openers Cameron Bancroft (21 not out) and Usman Khawaja (41 not out) completed the formalities in double quick time.
Apart from Sandhu and O'Keefe, who bagged 5 and 6 wickets respectively in both the innings, Bancroft was the star for the visitors with a crucial 150 in the first innings.
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Australia A rode on Bancroft's patient ton to post 349 in response to India A's 135 all out to clinch a vital 214-run lead.
Aparajith, with a five-wicket haul in the first innings, was the standout performer for the home team, which boasted of Indian Test skipper Virat Kohli in the playing XI.
Karun Nair's 50 in the first innings and opener Abhinav Mukund's fighting 59 in the second were also some of the notable contributions from India A players.
The Indian batsmen did put up a better show in their second innings on Day 3 but the top and the middle-order was guilty of not capitalising on starts to get big scores.
Kohli, Shreyas Iyer (49), Nair (31) and Naman Ojha (30) put up some resistance against a disciplined Australia attack only to let it slip eventually.
The first match between the two sides ended in draw.