Bhuvneshwar set an impressive tone with the new ball, claiming his 100th ODI wicket when he nipped one back to beat Aaron Finch in the third over, but left-armer Khaleel was less impressive and twice over-stepped in his opening spell.
The Aussies announced their playing XI and fast bowler Peter Siddle makes a return to the format after a gap of nine years.
Chasing the competitive target of 289, vice-captain Rohit Sharma displayed tremendous grit and waged a lone battle for India as the rest of the batsmen kept departing soon after their arrival to the crease.
The right-armer, now standing at 1.78m, was told throughout his junior career that he'd never make it as a fast bowler.
Both the teams have already played the T20I series and Test series on this tour.
The 27-year-old wicketkeeper-batsman has played just six previous ODIs and typically batted in the middle order, where he has scored 172 runs at an average of 34.40.
Aussie bowlers could find it hard to stop Indian batsmen from making inroads.
Khawaja scored 59 during his first ODI in nearly two years, fellow recalled batsman Handscomb top-scored with 73 while Marcus Stoinis smacked an unbeaten 47 off 43 balls.
But his mighty knock came to an end when he skied Marcus Stoinis to Glenn Maxwell at deep mid-wicket to end India´s remaining hopes.
Both batsmen failed to convince in the Test series.
The two spinners have played a huge role in Kuldeep Yadav and Yuzvendra Chahal over the last month as well.
The Aussie bowling attack do not possess the usual threat. Honestly, I got a bit carried away with the nature of the show.
It's an opportunity for Mohammed Shami to have a say and enhance his reputation.
It put huge brakes on the scoring even as Sharma and Dhoni struggled to get going.
Fact: When and where to watch the first ODI? . The match is scheduled to begin at 7.50 AM (IST).
India's ODI record in Australia is quite poor.
SonyLiv will stream the game live via the app and the website for the viewers in the Indian subcontinent.