Shane Watson muscled his way to 143 from 107 balls with six sixes and captain Michael Clarke, who had been in doubt for the match because of his recurrent back trouble, contributed 75 to Australia's 298 all out off 49.1 overs.
Mitchell Johnson, who was not required for the Ashes series won 3-0 by England, then bowled with raw pace and impressive accuracy to capture two for 21 from his 10 overs on an easy-paced pitch in England's 249 all out from 48 overs.
Ravi Bopara (62) and Jos Buttler (42) added 92 for the sixth wicket before Australia wrapped up the last international of the English summer to take the series 2-1 after two games were washed out.
Left-arm fast bowler Johnson, whose Test career has been plagued by inconsistency, again regularly exceeded 145 kms (90 miles) an hour.
His speed and bounce disconcerted all the top-order England batsman throughout the series and he must have forced himself into consideration when hostilities resume in the first Ashes Test of the return series starting in Brisbane on November 21.
Clarke told the BBC that winning the series had meant a lot to the Australian players after failing to regain the Ashes.
"I don't know whether it will have much impact on the Ashes back home but we get the flight back home tomorrow a lot happier as a one-day side, certainly," he said.
"The Ashes is still a way away but everyone is excited about that and the players are thinking about it already. But our focus has to be on the seven ODIs in India first."
England rested their leading bowlers James Anderson, Stuart Broad and Graeme Swann for the series and captain Eoin Morgan said the team management had learned a lot about the emerging players.
"The nature of the international schedule is that it's hectic. We prioritise Test cricket and with back-to-back Ashes series we have to be picky and choosy. But the next best guys here have done really well," he said.