Ben Stokes' final one-day international ended in another England defeat as South Africa won a sweltering series opener in Chester-le-Street by 62 runs.
The world champions, beaten 2-1 by India last week, were first worn down in the oppressive heat by Rassie van der Dussen's fine 134.
He combined with Aiden Markram, who hit 77 off 61 balls, in a controlled stand of 151, the backbone of the tourists' 333-5.
England reached 102-0 in response but lost their way against the Proteas spinners as the baked pitch tired.
Stokes, who announced on Monday that this match on his home ground would be his last 50-over international, was out lbw for five.
Joe Root made 86 from 77 balls but was bowled trying to hit out as the run-rate increased out of control.
After Root fell the final three wickets quickly followed and England were bowled out for 271 in 46.5 overs.
Victory gives South Africa a 1-0 series lead going into the second match on Friday at Emirates Old Trafford.
England's struggle in the sun
Including the Twenty20 series loss to India, this is England's fifth white-ball defeat in seven games over 12 days at the start of Jos Buttler's reign as captain.
South Africa's line-up may not be filled with superstars like India's but this victory was equally as convincing.
The conditions were difficult for players and spectators alike. As temperatures reached 38 degrees, players were seen using ice towels while members of the crowd required medical attention in the stands.
England bowler Matthew Potts only managed four overs on debut before having to leave the field because he was "struggling with effects of the heat".
With the bat, England did not seriously threaten to chase a good total.
Openers Jason Roy and Jonny Bairstow were unusually restrained before Roy hit spinner Keshav Maharaj to long-off for 43 and Bairstow was trapped lbw by Markram for 63.
Buttler also fell to spin, caught and bowled off a leading edge to Tabraiz Shamsi for 12, as England failed to bat out their 50 overs for the fourth ODI in succession.
Only Root offered any real resistance with a typically classy knock but, with wickets falling around him, England were never in the game.
Anrich Nortje, one of the fastest bowlers in world cricket, bowled the Yorkshireman as he swiped across the line before proving far too good for the lower order as he finished with 4-53.
Van der Dussen battles through
Despite the high score, South Africa's innings often felt low-key, not helped by the increased number of drinks breaks introduced because of the weather.
England struggled for wickets despite the return of leg-spinner Adil Rashid to their ranks.
South Africa opener Janneman Malan helped lay a platform with 57 from 77 balls before hitting Moeen Ali to deep mid-wicket and afterwards Van der Dussen largely accumulated through ones and twos rather than entertaining with boundaries.
Just 40 of the right-hander's runs came from hitting the rope, with no sixes in the whole South Africa innings.
Markram was marginally more aggressive in the pair's 20.2 overs stand. They both fell in the same over of Liam Livingstone spin - Markram caught at deep mid-wicket and Van der Dussen bowled trying to force a shot off the back foot - which helped England finish the innings well.
Only 46 came from the last six overs with Brydon Carse, the third Durham player in England's XI on their home ground, particularly effective - though the total still proved far out of England's reach.
Stokes bows out
Stokes is retiring from 50-over cricket because he says the intense schedule no longer allows him to play all three formats.
He looked emotional when given an ovation at the start of only his third England appearance on his home ground.
Potts' absence meant Stokes had to bowl more overs than expected and he was England's most expensive bowler.
He conceded six boundaries in his five overs, often hobbling - a sign of his fitness struggles that have played a part in his decision.
With the bat, Stokes was out to part-time spinner Markram, trying to reverse sweep his 11th ball.
The Riverside rose to its feet to applaud him off but it was a disappointing and premature end for an all-rounder unable to repeat his famous innings in the 2019 World Cup final.
'We never quite managed to impose ourselves' - reaction
England captain Jos Buttler on BBC Test Match Special: "We never quite managed to break that partnership and that really extended the game away from us. It was probably a good toss to win on a day like today where it was incredibly warm.
"With the bat we never quite managed to impose ourselves. South Africa bowled very smartly but we couldn't quite put enough pressure on them.
"We just haven't quite played to our potential yet this summer. But I'm not sure it is far away - it feels like we're getting back to where we need to be."
South Africa captain Keshav Maharaj: "The boys were really clinical today. Rassie set the tone with the bat and then the bowlers stuck really well to their plans."
Player of the Match Rassie van der Dussen: "We came into this tour knowing we'd have to play smart cricket. It's a big ground, we knew we would have to hit the gaps hard and run hard.
"Physically it was tough but we back ourselves and our fitness. We didn't hit a six, which I don't think I've ever seen! But it was a very good batting display."
