Australia set a daunting target of 441, riding on skipper Steve Smith's batting masterclass on a rank turner, and then skittled out the hapless hosts for a paltry 107 in 33.5 overs to take a 1-0 lead in the four-match series.
The embarrassing defeat also ended India's unbeaten streak of 19 Tests with the last defeat coming against England at Kolkata in late 2012.
The 32-year-old O'Keefe did the star turn once again with identical figures of 6/35 in both innings as India failed to even cross 110 in both innings.
Skipper Virat Kohli had a rare bad Test match where he had scores 0 and 13 in both innings of the game. India collectively posted their lowest aggregate for a home Test match and ended up suffering their second biggest defeat at home in terms of runs.
Kohli was out in the second innings shouldering arms to an angled delivery from O'Keefe which dashed India's minuscule hopes of a miraculous comeback.
After Smith's superb 109 -- his 18th Test ton on a spiteful pitch --, there was no comeback for India as both openers KL Rahul and Murali Vijay made a mess of DRS when it was the umpire's call.
(REOPENS DEL 7)
The Indian batsmen, similar to the first innings, had no clue on how to tackle 32-year-old O'Keefe, who had his finest hour in international cricket.
Neither could they properly negotiate wily Nathan Lyon (4/53) as both made life miserable for the Indian batsmen.
After the 7/11 debacle in the first innings, the second innings saw India lose 6 for 8.
Earlier, Australia - having taken a commanding first innings lead of 155 by scoring 260 and then bundling out the hosts for a paltry 105 - rode on captain Stephen Smith's lucky and plucky first-ever century on Indian soil (109) to make 285 before they were dismissed at the end of the first session which was extended.
India crashed from 89 for five to 107 all out in under ten overs.
Vijay and Rahul both were trapped leg before, by O'Keefe and Lyon respectively and also foolishly decided to go in for DRS when both appeared to be caught plumb in front, leaving India without any DRS calls after 5.3 overs when they had slumped to 16 for 2.
While Vijay was deceived by a straight ball, Rahul played back to be low on the pads and both were instantly given out before asking for DRS.
Rahane was out on the drive, caught by Lyon diving forward at short covers, to give O'Keefe his third wicket of the innings and ninth of the game.
And to make matters even more hopeless for the hosts, Ravichandran Ashwin was out leg before to O'Keefe. Ashwin was given not out by the umpire before Australia pressed for DRS and got the verdict reversed in their favour.
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