Morne Steyn and Jean de Villiers touched down as a second-half South African barrage broke England's resistance 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 Farrell penalties applying pressure.
Ben Foden claimed a late England consolation after the final hooter and head coach Stuart Lancaster will take some 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.
The scoreline might have been close but the normally reliable Steyn, who still scored 17 of his side's points, did miss two conversions and a penalty.
Heavy rain eased before kick-off but the surface remained slick. The Springboks looked to impose themselves early on with some powerful hits and the more expansive handling of the two sides.
Bryan Habana gave England an early warning as he claimed a high kick from scrum-half Ben Youngs and weaved his way through several failed tackles before being halted on halfway.
But England also went hard into their tackles and initially held firm, albeit at a price as Durban-born centre Brad Barritt was forced off with a head injury.
Midway through the second half JP Pietersen almost found a way through on the left but was pushed into touch by Mike Brown, an act the South Africa wing took exception to by sparking a minor fracas.
South Africa continued to pour forward with Habana proving a tricky customer. Eventually England had to crack and it was De Villiers who broke through for a second try on the hour as he raced on to a Pietersen pass and powered through a Brown tackle.
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