New Zealand (0) 7
Tries: Roigard Cons: Mo'unga
South Africa (14) 35
Try: Kolisi, Arendse, Marx, Mbonambi, Smith Cons: Libbok 5
New Zealand lock Scott Barrett was sent off as the All Blacks suffered the heaviest defeat in their history.
Barrett received two yellow cards, with the second for a reckless clearout to the head of hooker Malcolm Marx being referred to the TMO 'bunker'.
South Africa went ahead through Siya Kolisi and Kurt-Lee Arendse scores, before second-half tries from Marx, Bongi Mbonambi and Kwagga Smith.
The All Blacks' previous record loss was by 21 points in 1999 and 2019.
At a packed-out Twickenham, Barrett received his first yellow card after multiple team infringements as the All Blacks struggled to contain the relentless power game of the Springboks.
He returned from the sin-bin but just before half-time shoulder-charged into Marx, who was close to the ground at a breakdown, leaving referee Matthew Carley no decision but to send him off.
New Zealand have already lost experienced lock Brodie Retallick for the opening game of the World Cup against France on 8 September with an injury, as Barrett becomes the first All Black to be sent off twice.
Tyrel Lomax's World Cup could also be at risk after the prop left the field early with a nasty knee injury.
The world champions made it back-to-back wins after their 52-16 demolition of Wales in Cardiff last weekend, as Jacques Nienaber's side appear to be hitting their best form before their World Cup opener against Scotland on 10 September.
The win also ends New Zealand's 11-match unbeaten run as South Africa's power game - so successful during the 2019 World Cup - proved too much for their 14-man opponents.
"You couldn't help but be impressed with what they did, they really got stuck into us," said All Blacks coach Ian Foster.
"Their physicality and their set-piece was superb and they had a massive game at scrum and line-out time. That was a big difference."
Springboks peaking at right time
Twickenham was an unusual ground to host the two southern hemisphere sides, with their last meeting at the venue coming in a 2015 World Cup semi-final, which the All Blacks won 20-18 thanks to a late Beauden Barrett try.
Since lifting the Webb Ellis Cup in 2019, the Boks have shown glimpses of the relentless power and kicking game which dominated England in the final.
During the opening period that game returned, with the All Blacks unable to find any foothold in the contest, losing both Scott Barrett and captain Sam Cane to early sin-bins.
The pressure eventually told as Kolisi smashed his way over the line aided by the huge frame of lock Eben Etzebeth - in only the captain's second game back since knee surgery following ligament damage in April.
Wing Arendse then doubled the lead, intercepting Jordie Barrett's pass to run in untouched.
Sharp play at the front of the line-out saw Marx go over for the Boks' third before the famous 'Bomb Squad' of front-row replacements was released early in the second period.
They entered the game alongside three other replacements in the forwards, and the almost all-new pack dismantled the All Blacks with further scores resulting from line-outs for Mbonambi and Smith.
"It was a very good start for us, a great performance by the team," man of the match Damian Willemse told Sky Sports.
"This will give us some momentum going into the Rugby World Cup. I am the man of the match, but credit to the forwards, they put in a hell of a shift."
It wasn't all about the forwards as 20-year-old Canan Moodie - in his first start at centre - provided brilliant touches throughout the game, one being a disallowed solo try.
The only positive for New Zealand was replacement scrum-half Cam Roigard grabbing a well-taken score - his first for his country - in the final ten minutes.
If Ireland fail to beat Samoa on Saturday, South Africa will head to France as the number one ranked side in the world.
New Zealand would have gone to number one if they had won by 15 points, which they managed during the Rugby Championship, but instead will be reassessing their game after a chastening defeat.
"I think both teams needed that game, we certainly did," added Foster. "We lost the cohesion when we were put under pressure, but I thought our defence in the first 20 minutes was outstanding and if we had more discipline in key areas we could have counter-punched."
New Zealand: B. Barrett; Jordan, R. Ioane, J. Barrett, Telea; Mo'unga, Smith; De Groot, Coles, Lomax; S. Barrett, Whitelock; Jacobson, Cane (capt), Savea.
Replacements: Taukei'aho, Williams, Newell, Vaa'i, Lord, Papali'i, Roigard, Lienert-Brown.
South Africa: Willemse; Arendse, Moodie, Esterhuizen, Mapimpi; Libbok, De Klerk; Kitshoff, Marx, Malherbe; Etzebeth, Mostert; Kolisi (capt), Du Toit, Vermeulen.
Replacements: Mbonambi, Nche, Nyakane, Kleyn, Snyman, Van Staden, Reinach, Smith.
Referee: Matthew Carley (RFU)