Bairstow slammed a 92-ball 139 and Hales took the same amount of deliveries to amass a quickfire 149 runs.
It looked as though England would surpass the 500-run mark, as captain Eoin Morgan joined in the fun with a 21-ball half century - the fastest ever by an English ODI batsmen, before Hales brought up the world record with a massive six off Jhye Richardson to the delight of a sell-out crowd.
The hosts sealed five-match series with a 242-run victory, which is Australia's largest defeat as well. England opening pair of Alex Hales and Jonny Bairstow added 159 runs together before Roy was dismissed for 82. Only once in the history of List A cricket.
For Bairstow, in magnificent form, it was his fourth ODI century in six innings and his sixth in 19 since his recall less than a year ago. The pitch is unlikely to allow the sort of free-scoring that England managed in Nottingham and the highest score in the Royal London One-Day Cup at the Riverside was 299.
After a match where England scored 481, smashing the previous highest total by 37 runs, Langer compared England's batting line-up to the Australian side that won the 2003 and 2007 World Cups, led by Adam Gilchrist, Matthew Hayden and Ricky Ponting.
There was no let-up in the astonishing run-rate, however, as Bairstow - who had two scares, overturning an lbw verdict against him on 27 and then escaping a very hard chance to Marcus Stoinis at deep mid-off three runs later - powered on to a 69-ball century.
Morgan hit six of them and, for good measure, went past Ian Bell as England's all-time record ODI runscorer. The wheels fell off for Australia.
481 - England's epoch-making total for the loss of just six wickets.
But he soon had a say with the ball - first tumbling low at mid-on to collect Short's chip off David Willey to mid-on and then seeing off Travis Head caught-and-bowled just after the opener had reached a 36-ball 50.
England notched their 2nd consecutive ODI series win against the world champions.
Australia, however, were gifted a wicket when Roy ran himself out going for a needless second run.
"The wicket was still terrific when we batted on it as well".
The potency of the spinners has been one of most striking differences between the teams, with England claiming 15 dismissals through spin and Australia just one. "Their top three are brutal".