Hughes was the highlight of a free-scoring Australian innings with skipper George Bailey scoring 89 off 79 balls and David Hussey chipping in with a late unbeaten 60 off 34 balls.
Hussey, the younger brother of veteran Mike Hussey, finished with a flourish, plundering 21 runs off the last over from off-spinner Ajantha Mendis, including a six over long-off to bring up his half-century.
There were a couple of failures in the Australian innings with Usman Khawaja run out for three after setting off for a risky single and being sent back by Hughes.
Fellow top-order debutant Aaron Finch went for 16 and Glenn Maxwell was caught attempting to chip over the on side off Nuwan Kulasekara for five.
Paceman Lasith Malinga didn't fare well on his return for Sri Lanka taking 1-61 on a pitch suited for batting.
Australia rested opener David Warner, skipper Michael Clarke, injured vice-captain Shane Watson and wicketkeeper Matt Wade, while Mike Hussey, newly-retired from Test cricket, was dumped after announcing this will be his final international season.
It is the most first-gamers Australia have fielded in an ODI game since January 1986 when Simon Davis, Dave Gilbert, Bruce Reid and Steve Waugh made their debuts.