However, South Africa climbed off the canvas, Faf de Klerk plunging over from close range before Nkosi's brace, although the first owed much to Daly's failure to deal with a bouncing ball inside his own in-goal area.
The Springbok wing had a second try moments later, South Africa showing fine handling through midfield before a pass inside released Nkosi to fly over. Maro Itoje and Jonny May scored late tries for a deflated England but could not prevent Jones's side slipping to another uncomfortable defeat.
South Africa had their first points on the 10-minute mark, with Pollard sending over a penalty but a second try for England soon after continued their dominant start.
England suffered a fourth straight test loss and fifth overall.
New Springboks coach Rassie Erasmus is one for one after beating England at Ellis Park.
Kiwi-born flanker, Hurricanes captain Brad Shields, endured a rough start to his worldwide career for England.
There was a landmark moment for Brad Shields late in the first half, the forward coming on for his England debut after just 35 minutes for lock Nick Isiekwe.
The game had appeared to be all over inside the opening quarter as England stormed into a 24-3 lead thanks to three quick-fire tries from Mike Brown, Elliot Daly and Owen Farrell, all converted by Farrell, plus a monster 61-metre penalty from Daly. Farrell slotted a penalty to end a pulsating first 29-27 in favour of the home side. Pollard extended South Africa's advantage with a penalty, though the fly-half's effort was sandwiched between two misses that kept England in touch.
Springboks 42 - Tries: Faf de Klerk, Sbu Nkosi (2), Willie le Roux, Aphiwe Dyantyi.
Crucially, a yellow card to England loosehead Mako Vunipola, playing in his 50th Test, saw the visitors reduced to 14 men in the 63rd minute.
Following another seven points from the hosts after a converted Dyantyi try with de Klerk once again pulling the strings, Mario Itoje just went over the line from the scrum with ten minutes left, with the failed conversion from Farrell keeping the hosts' lead at seven, 39-32.
The final score of an exhilarating match was a slim 42-39 victory for South Africa at England's expense. England set up for one last attack from a lineout, but South Africa stole the throw-in and scrambled the ball out of play to clinch victory.