Victory in this day/night fixture yesterday left world champions Australia 6-0 up and on course to complete the first ever 7-0 clean sweep in a bilateral series in Sundays finale at Durhams Riverside ground.
Paines 111 was the cornerstone of Australias 296 for eight as the holders continued to warm-up in style for next weeks start of the Champions Trophy tournament in South Africa.
England, chasing 299 to win, collapsed to 60 for four inside 15 overs. They were eventually dismissed for 185, with nine overs to spare as they suffered their 11th heaviest defeat, in terms of runs, in 517 one-day internationals ODIs.
No England batsman made more than number eight Tim Bresnans 31 not out.
Wicketkeeper Paine, an opener in the one-day format, reached three figures in only his seventh match at this level.
Together with Michael Hussey 65, Paine - who only made his one-day international debut against Scotland in Edinburgh last month - put on 163 for the third wicket after the duo came together with Australia 40 for two.
Fast bowler James Anderson, back in the England side after being rested for two matches, returned fine figures of four for 55 before running out Brett Lee for nought with a direct hit from long-on.
Paines match got even better off only the second ball of Englands reply.
England captain Andrew Strauss appeared to have swayed out of the way of a Lee bouncer in near textbook fashion, the ball brushing his shoulder on the way through to Paine.
But Pakistani umpire Asad Rauf, after a prolonged appeal, gave Strauss out to the visible disbelief of the left-hander and England were nought for one.
Joe Denly drove James Hopess second ball for six but the medium-pacer had his revenge when, off his 11th delivery, the Kent opener skied him to Lee.
Australia captain Ricky Ponting, long one of the worlds best outfielders emphasised Australias all-round superiority with two magnificent direct hit run-outs to dismiss Matt Prior and Ravi Bopara.
After Ponting had called correctly to end Strausss streak of five straight toss wins, Anderson made a double breakthrough.
He had Shane Watson playing on and then made it two wickets for seven runs in 16 balls when he had Ponting hooking straight to Ryan Sidebottom at deep backward square leg.
But Englands joy at removing Ponting for six, 120 fewer than he managed in Australias four-wicket victory here on Tuesday, was short-lived as his fellow Tasmanian Paine unfurled a fine array of strokes.
The 24-year-old Paine, only playing after first-choice keeper Brad Haddin was ruled out of the series with a broken finger that will also sideline him from the Champions Trophy, had made his maiden ODI fifty at Lords on Saturday.
Here he advanced into the 90s when he flicked left-arm quick Sidebottom off his pads for a four which split the fielders at deep square and fine leg.
His single off Graeme Swann saw him to a hundred off 130 balls, including a superb straight six off Dimitri Mascarenhas and 13 fours.
Paine was eventually dismissed when expertly caught by opposing gloveman Prior, standing up to the stumps, after getting a bottom edge off Mascarenhas.