Morne Steyn and Jean de Villiers touched down as a second-half South African barrage broke England's resistance to claim a 22-17 victory in the first Test in Durban.
England met the Springboks challenge head on at Kings Park and were level at 6-6 at half-time after Owen Farrell and Steyn traded penalties.
South Africa began to gain the upper hand after the break as Steyn and captain De Villiers broke through and the hosts held on despite two more Owen Farrell penalties applying pressure.
Ben Foden claimed a late England consolation after the final hooter and head coach Stuart Lancaster took heart from the fighting display of his players.
Despite that, what was England's eighth successive Test loss to the Springboks still leaves them facing an uphill fight to win their first three-match series in South Africa.
Lancaster said: "I was happy with the endeavour and the effort we put in from the first minute until the 80th minute.
"Very positive first-half performance, accurate in a lot of areas and it was that third quarter where the Springboks got on top of us a bit and it's very hard when they get that momentum.
"(The players are) disappointed because it's one we could have won."
Captain Chris Robshaw told Sky Sports 2: "We went in 6-6 at half-time, we came out all guns blazing but unfortunately they got an early score and managed to build pressure on us.
"South African sides, you always know they're going to be very physical but if you looking at the game we were never more than a score away but unfortunately we were the wrong side of that score.
"We have to start building for next week, there's been a lot of positives and a couple negatives you can pick out."