South 346 for 6 (Northeast 118*, Dawson 83, Malan 78) beat North 299 for 9 (Bresnan 74, Duckett 64) by 47 runs
Sam Northeast hit a fine unbeaten century as the South clinched the new North-South Series with a match to spare thanks to a 47-run victory at the Dubai International Cricket Stadium.
Northeast, the Kent captain, made an unbeaten 118, and shared the match-winning partnership of 170 with Liam Dawson, as the South piled up 346 for 6 after being put in by North captain Keaton Jennings - with Dawid Malan adding an authoritative 78 to the unbeaten century he scored in the opening game on Thursday.
Ben Duckett gave the North the flying start they needed in reply, racing to a 32-ball half century and sharing a third-wicket stand of 74 with Liam Livingstone which contained the most absorbing cricket of the series.
But after Toby Roland-Jones had Livingstone well caught by Steven Finn off a top-edged hook, Dawson claimed the key wicket of Duckett for 64, and the Hampshire allrounder went on to earn figures of 2 for 46 in his second tidy spell of the series - although they were slightly dented by Tim Bresnan, who thumped a typically defiant 74 from 66 balls to reduce the North's margin of defeat.
The South will now be aiming for a 3-0 whitewash when the series concludes in Abu Dhabi on Tuesday.
Both sides made two changes from the first game, with Tom Alsop and Tim Groenewald replacing Lewis Gregory and Mason Crane for the South, and Josh Poysden and Saqib Mahmood making their North debuts as Mark Wood and Graeme White took a rest.
Bresnan gave the North the perfect start after Jennings had chosen to field in roasting heat, opening up with a maiden which ended with Daniel Bell-Drummond edging a drive to Joe Clarke.
That was the first wicket the South had lost in the series and after watching Malan and Bell-Drummond seal a 10-wicket win on Thursday their captain James Vince made an immediate impression as he stroked 46 from 41 balls in a second-wicket stand of 113 with Malan.
But the North's spinners pegged back the South, with Vince bowled by Livingstone, Poysden bowling a tidy eight-over spell, and Yorkshire's Jack Leaning claiming the wickets of Malan and Alsop in consecutive overs with his occasional off-spin.
That left the South under pressure for the first time in the series at 142 for 4. But Dawson joined Northeast to strike 83 from 68 balls with five fours and three sixes.
He holed out to long-off, giving Harry Gurney his first wicket of the series, but Northeast moved on to his third List A century, seizing his first chance to impress the England head coach Trevor Bayliss who was again watching with selectors James Whitaker and Mick Newell.
Finn and Tom Curran claimed early wickets when the North replied under the floodlights, Sam Hain edging Finn to Ben Foakes, and Curran pinning his England Lions captain Jennings lbw.
Curran's second ball at Livingstone was a no-ball which the Lancashire right-hander edged wide of second slip for four - and he then dispatched the free hit over extra cover for six into the corporate seats.
Livingstone added a second six over long leg off Finn, while Duckett combined improvisation with some more orthodox shots in hitting nine fours and a six.
But their dismissals left the North with a mountain to climb, and despite promising starts from Clarke and Leaning, only Bresnan played an innings of substance - and by then it was far too late.