England, fresh from their 481 for six -- the highest men's ODI total of all time -- in a crushing 242-run win at Trent Bridge on Tuesday, 'only' needed 311 at the Riverside.
But what was still England's second highest total batting second to win a match at this level, behind their 350 for three against New Zealand at Trent Bridge three years ago, was made to look insignificant as in-form openers Roy (101) and Jonny Bairstow (79) put on 174.
England finished on 314 for four, with Jos Buttler 54 not out as they won with 32 balls to spare.
England, the world's top-ranked side in this format, will now look to surpass their previous best ODI series result against world champions Australia -- 4-0, including a washout, in a five-match home campaign in 2012 -- at Old Trafford on Sunday.
This was Australia's 15th defeat in 17 completed ODIs as once again a side missing six first-choice players in banned star batsmen Steve Smith and David Warner, as well as injured quicks Mitchell Starc, Pat Cummins and Josh Hazlewood and sidelined all-rounder Mitchell Marsh, failed to truly extend 2019 World Cup hosts England.
Roy, who ran himself out for 82 on Tuesday, was quickly into his stride with two fours off successive Billy Stanlake deliveries.
Bairstow greeted Nathan Lyon's first delivery of the series by forcing the recalled off-spinner through the covers for four.
Roy, following a 120 in the first ODI at The Oval, his Surrey home ground, completed another hundred when he hoisted Lyon for a huge six over long-on that saw him to the landmark in 83 balls.
But two balls later his sliced drive off Lyon found Shaun Marsh at backward point.
And 174 for one became 183 for two when Bairstow, trying to run Stanlake to third man, guided a catch to Australia captain and wicket-keeper Tim Paine.
But Australia's series was summed up when Alex Hales, on 17, edged medium-pacer Michael Neser only for Paine to drop a regulation two-handed catch that came straight to him.
Earlier, Aaron Finch (100) and Marsh (101) both hit hundreds in Australia's 310 for eight, with Marsh's following his 131 against England in Cardiff last weekend.
But their failure to press on cost Australia a truly imposing total.
Their score was still a Riverside ODI record, surpassing England's 307 for five against New Zealand in 2008.
Fast bowler Mark Wood took two wickets in an over on his Durham home ground before left-arm paceman David Willey grabbed three in five balls on his way to figures of four for 43.
Paine, who fielded first at Nottingham, unsurprisingly opted to bat when he won Thursday's toss.
Finch and Travis Head (63) got Australia off to a sound start and thet were well-placed at 225 for one come the start of the 40th over.
Yet they were three wickets down when it ended.
Wood broke a partnership of 124 when Finch was lbw to a ball that cut back, before he bowled Marcus Stoinis in similar fashion.
Marsh launched leg-spinner Adil Rashid for six to complete his hundred.
But a ball after Alex Carey holed out off Willey, Marsh fell when he found Roy at long-on who, before he stepped over the boundary, reverse-flicked the ball back several yards to Overton, who completed an extraordinary catch.
Paine survived the hat-trick, but two balls later Neser was caught behind off Willey.
Aaron FinchAlex HalesChester-le-Street ODIEngland vs AustraliaEngland vs Australia 2018jason royJonny BairstowMichael NeserNathan Lyonshaun marshTim Paine
First Published: June 22, 2018, 2:30 AM IST