Dawid Malan and Daniel Bell-Drummond posted an unbroken stand of 205 as South crushed North by 10 wickets in Dubai.
The North-South fixture was making its return to the calendar for the first time since 1961, now as a three-match 50-over series rather than a first-class encounter, with England head coach Trevor Bayliss casting his eye over proceedings.
He cannot have failed to be impressed by Malan's 109 not out and Bell-Drummond's 92no, knocks that made light of North's 202 all out.
A North side captained by Keaton Jennings and led by England bowling coach Ottis Gibson opted to bat first, only to be dismissed in 43.3 overs for an underpowered total.
Ben Duckett fell to Tom Curran before Jennings and the in-form Liam Livingstone were mopped up by Toby Roland-Jones.
Opener Sam Hain managed 33 before a bright stand of 63 between Joe Clarke (57) and Tim Bresnan (40) added some substance to the middle order.
But it was not enough as South, guided by Bayliss' number two Paul Farbrace, continued picking up regular wickets. Recent England call-up Curran claimed three for 19 and left-arm spinner Liam Dawson great control en route to two for 29.
Highly-rated leg-spinner Mason Crane struck twice but also suffered more than most in conceding 72 runs.
Malan and Drummond proved more than capable of reeling in the runs, crossing the line with 99 deliveries unbowled.
Between them the duo hit 27 fours and three sixes, having successfully seen off an early examination from Mark Wood and Bresnan, the latter seeing Malan dropped in his first spell.
Wood, on his first competitive outing since an ankle operation last autumn, finished with nought for 45 in seven overs.
The next game takes place in Dubai on Sunday, with North needing a win to stay in the series.