Four rain delays that totalled three hours and 40 minutes caused havoc during India's substandard innings at Optus Stadium.
Under the Duckworth-Lewis-Stern method, Australia require just 131 from 26 overs.
If rain stops Australia's innings from reaching 20 overs, the match will be deemed a wash-out.
Both captains wanted to bowl first under the overcast conditions, and it was Australia skipper Mitch Marsh who had the coin toss go his way.
It didn't take long for Australia's pace attack to muscle in on India's top order.
Rohit Sharma (8) was the first to fall when he was caught at second slip off the bowling of Josh Hazlewood (2-20 off seven overs).
Indian fans erupted when 'King' Kohli strolled out to the crease, but the veteran superstar lasted just eight balls before striking Mitchell Starc (1-22) to a diving Cooper Connolly at gully.
Alarm bells were ringing at 3-25 when Shubman Gill (10) was caught behind after tickling Nathan Ellis's first delivery down the leg side.
A 12-minute rain break gave India a short respite, and players were forced off again - this time for more than two hours - with the score 3-37.
Shreyas Iyer struck Hazlewood for four upon the resumption, but he was out a short time later when he gloved the Aussie paceman down the leg side for Josh Philippe to take another diving catch, reducing India to 4-45.
Handy runs from KL Rahul (38 off 31 balls), Axar Patel (31 off 38 balls) and debutant Nitish Reddy (19no off 11 balls) finally got the scoreboard ticking, but it wasn't nearly enough to set a competitive total.
Matt Renshaw took three catches in his ODI debut, while fellow debutant Mitch Owen snared 2-20.
The ODI series is likely to mark the final international appearances in Australia of veteran Indian stars Kohli and Sharma.
The duo are retired from Test cricket and T20 internationals, and there's doubt about whether they will be able to make it to the 2027 ODI World Cup in Africa.
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