The tourists are just one win away from claiming a 7-0 sweep of the tournament after Paine scored 111 to steer Australia to 8-296 from 50 overs and some trademark sharp fielding by Ricky Ponting helped restrict England to a total of 185 with nine overs to spare.
Paine was well supported by Michael Hussey, who hit 65 off 69 balls and the pair put on a 163-run stand for the third wicket.
In the side as a replacement for injured wicketkeeper Brad Haddin and playing just his seventh one-day international after making his debut against Scotland last month, Paine faced 148 balls for his score, which included 14 fours and one six.
The baby-faced 24-year-old more than doubled his previous best of 51, reached last Saturday at Lord's, where Australia clinched the series 4-0.
In his latest knock, Paine steadied the innings after fellow opener Shane Watson (four) and Ponting (six) fell cheaply.
He heaved a Dimitri Mascarenhas delivery for six over long-off to move within one run of his half century and brought up 50 with a well-guided single to third man.
Hussey smashed a six off Ryan Sidebottom over midwicket before bringing up his half century with a single off the next ball.
As he ran through for a single to bring up his ton, Paine whipped his bat through the air and pumped his fist before embracing Hussey.
A short time later, Hussey cleared the fence again, lofting Mascarenhas over midwicket.
But he fell chasing a similar placement off the bowling of spinner Graeme Swann and was caught by Joe Denly.
Paine got an outside edge to a Mascarenhas delivery and was caught behind by Matthew Prior.
Anderson, who took 4-55 off 10 overs, also dismissed dangerous batsmen Callum Ferguson (six) and Cameron White (35) and ran out Brett Lee for nought.
James Hopes, in for a resting Michael Clarke, contributed a quick-fire 38 off 22 and claimed 3-32 off nine overs to be the pick of the Australian bowlers.
Two spectacular run-outs by Ponting cleaned up England's top order after they were unlucky to lose Andrew Strauss on the second ball of the innings, caught behind for no score by Paine off a Brett Lee ball that hit nothing but the batsman's shoulder.
Pointing narrowly missed a chance to run out Prior, who had to dive to make his ground.
But the Australian captain didn't miss when Ravi Bopara nudged Nathan Bracken to extra cover and set off before deciding against the run.
Ponting collected the ball and, while pivoting, threw down the stumps to dismiss a backing up Prior.
In the following over, Ponting swooped on Bopara's shot to midwicket and hit at the non-striker's end to with Bopara well out of his ground.
From there, none of England's batsmen managed to fire, with tailender Tim Bresnan's unbeaten 31 their highest score.
