Yadav took five for 18 as Australia collapsed to 34 for six wickets by the end of the 12th over and were eventually bowled out for a paltry 65 in 23.3 overs.
Gangly paceman Ishant Sharma supported Yadav well by taking three wickets for just 11 runs in his five overs.
Before that, India rattled up a challenging 308 for six as Karthik smashed an unbeaten 146 and added 211 runs for the sixth wicket with skipper Mahendra Singh Dhoni (91).
India scored exactly 100 runs in their last 10 overs as Australia failed to turn the screws after polishing off five top Indian wickets for only 55 runs at the Swalec Stadium.
It was India's second consecutive win, having beaten Sri Lanka earlier and it gives them the confidence ahead of their tournament-opener against South Africa on Thursday.
Yadav bowled at the right lengths as Australian batsmen played loose strokes too early in the innings. Matthew Wade (5) and Phil Hughes (14) were bowled playing across the line to fuller balls while David Warner (0) was caught at first slip playing an expansive drive.
Australia missed their injured captain Michael Clarke as stand-in skipper George Bailey (1) was beaten by pace and late movement while the in-form Shane Watson (4) dragged the ball onto his stumps while trying to cut.
Mitchell Marsh (0) got a faint inside edge that landed in the keeper's gloves as the Australian procession confounded pundits of the game.
Except Hughes and Adam Voges (23 off 49 balls), none of the top seven batsmen got into double digits.
Earlier, Like India's first warm-up game, the lower middle-order batsmen saved the blushes with both Karthik and Dhoni magnificently pacing their innings on a track that had plenty for the batsmen. Their stand came off 191 balls.
Karthik faced 140 balls and hit 17 fours and a six while Dhoni took 77 balls for his knock, laced with 10 boundaries, including four sixes.
Karthik's back-to-back centuries, he scored an unbeaten 106 in Birmingham against Sri Lanka, will help him improve his chances for a slot in the playing XI when begin their campaign on Thursday.