Rassie van der Dussen's century helped South Africa spoil Ben Stokes's farewell to one-day international cricket as the Proteas won by 62 runs on the England star's Durham home ground to go 1-0 up in a three-match series.
Van der Dussen's career-best 134 was the cornerstone of South Africa's 335-5, their highest ODI total in England.
He also shared stands of 109 with opener Janneman Malan (57) and 151 with Aiden Markram, who made a stylish 77.
Test captain Stokes did not have a fairytale finish to a 50-over international cricket career that peaked with a player of the match display in England's 2019 World Cup final triumph.
The struggling 31-year-old paceman took an expensive 0-44 in five overs amid searing heat, after being cheered by his loyal home fans as he led England onto the field.
Stokes then made just five with the bat before he was lbw to off-spinner Markram, having missed a reverse sweep.
Stokes had announced on Monday that this game would be his 105th and last match at this level, with the dynamic all-rounder saying a congested England fixture schedule meant he had to jettison ODIs in order to still give of his best in Tests and Twenty20s.
'We will miss Stokes'
Fellow World Cup-winner Jos Buttler, now England's white-ball captain, thanked Stokes for his ODI efforts.
"Three years ago (the 2019 World Cup final) will live long in the memory but every day he turns up, whether that be for training or in a match, he puts in 100 percent.
"He has been a fantastic ambassador for us in ODI cricket. We will miss him."
Joe Root took up the charge after Stokes's dismissal with a run-a-ball fifty.
But a target of 103 off the last eight overs, with England already six wickets down, was too much even for the world's top-ranked Test batsman.
Root was eventually bowled for an excellent 86 by express quick Anrich Nortje, who finished with 4-53 from 8.5 overs.
"The boys were really clinical today," South Africa captain Keshav Maharaj told Sky Sports. "Rassie set the tone with the bat and then the bowlers stuck really well to their plans so full credit to everyone for their performances."
On a day where temperatures touched 37-degrees, it was no surprise Maharaj, skipper in place of the injured Temba Bavuma, opted to bat first after winning the toss.
"We didn't expect a heatwave in England to quite be this hot, it was quite nostalgic, like being at home!," said Maharaj.
Conditions, however, took their toll on England ODI debutant Matthew Potts, called up after the recent 2-1 series loss to India, who bowled just four overs before leaving the field due to the heat.
England openers Jason Roy (43) and Jonny Bairstow (63) had launched the 50-over world champions' chase with a partnership of 102 in 19 overs.
But that stand ended when Roy chipped left-arm spinner Maharaj and David Miller, running round from long-off, held a good low catch.
Bairstow, reprieved when Lungi Ngidi dropped a routine chance at long leg, was lbw soon afterwards on the sweep to Markram (2-25).
Slow bowling also proved the undoing of Buttler, caught and bowled for 12 by left-arm wrist-spinner Tabraiz Shamsi.
Buttler, proud of the way England fielded in the extreme heat, said: "We just couldn't quite find those breakthroughs, couldn't break that fantastic Van der Dussen-Markram partnership. In the chase, we never managed to quite impose ourselves with the bat."
Earlier, van der Dussen's leg-glanced boundary off Curran saw him to a 90-ball hundred including nine fours. It was the 33-year-old's third century in 36 ODIs and first against England.
He surpassed his previous highest ODI score of 129 not out against India at Paarl in January this year before he was bowled by a Liam Livingstone delivery that kept low two balls after the spinner dismissed Markram.
The series continues at Old Trafford on Friday.