Dawid Malan made a high-class century and shared an unbroken opening partnership of 205 with Daniel Bell-Drummond as the South crushed the North by 10 wickets in the first game of the North-South Series in Dubai.
The North were dismissed for 202, with three wickets for Tom Curran and two each for Toby Roland-Jones, Mason Crane and the especially impressive Liam Dawson in a fine all-round bowling performance by the South team.
Malan and Bell-Drummond made short work of the modest target, with more than 16 overs remaining as the Middlesex left-hander sealed victory with his 16th four.
Malan, who was included in an England T20 squad last summer, also hit a six as he ended unbeaten on 109 from 103 balls, while Bell-Drummond hit two sixes and 11 fours to reach 92 from 98 deliveries.
The North suffered an early blow after their captain Keaton Jennings chose to bat first, when Curran (3-19) claimed the scalp of Ben Duckett, edging a drive to Ben Foakes on eight.
Curran took 1-16 in his opening burst and Roland-Jones (2-23) kept up the pressure in an excellent seven-over spell in which he earned the key wickets of Jennings (15) and Liam Livingstone (10).
Jennings steered to Malan at slip, and Livingstone, after launching Lewis Gregory into the stands for the first six of the series, was brilliantly caught by Curran running back from mid-off as he aimed for another big hit.
Sam Hain survived a couple of dropped chances to make 33 from 55 balls until he was undone by the introduction of Mason Crane, lbw sweeping against the spin.
Then Jack Leaning (9) ran himself out trying to take a second to Crane at deep cover, leaving the North in deep trouble at 91-5.
Bresnan joined Joe Clarke in a counter-attacking sixth-wicket stand of 63 in 10 overs, striking three sixes in making 40 off 41 balls.
But the Yorkshireman was bowled behind his legs trying to reverse sweep Dawson, the Hampshire all-rounder who bowled his 10 overs straight through to earn excellent figures of 2-29.
Clarke, who struggled for runs in the England Lions' recent one-day series in Sri Lanka, made a welcome return to form with a 49-ball half-century including five fours and two sixes off Crane.
But he was bowled for 57 aiming an ambitious ramp shot at the first ball of Curran's second spell, triggering a lower-order collapse as the North's last four wickets tumbled for nine runs inside three overs.
Durham all-rounder Paul Coughlin was Dawson's second victim, lbw for 19 which included two cleanly-struck leg-side sixes.
Then Curran deceived White (2) with a change of pace to take a return catch, and finally Crane returned to have Harry Gurney (5) snapped up at slip by Malan.
Malan and Bell-Drummond survived a searching new ball examination from Mark Wood and Tim Bresnan, Wood bowling a total of seven overs in two spells his first competitive action since an ankle operation last autumn, and Bresnan having Malan dropped in his third over.
But after that they were rarely troubled, although Northamptonshire left-arm spinner Graeme White claimed the small consolation of bowling the only maiden of the match in the penultimate over.
The match was watched by England coach Trevor Bayliss as well as selectors James Whitaker and Mick Newell, with assistant coach Paul Farbrace enjoying an initial triumph over fast-bowling coach Ottis Gibson - whose North team now need to win the second match, also at the Dubai International Cricket Stadium on Sunday, to stay alive in the three-match series.