South Africa beat England by an innings and 12 runs on Monday in the first test at the Oval.
Dale Steyn took 5-56 and Imran Tahir claimed 3-63 as England slumped from 203-5 to 240 all out during the afternoon session on day five.
Ian Bell and Matt Prior had given England hope of saving the match with a stand of 86, but England collapsed after Prior fell for 40 trying to sweep Tahir.
Steyn claimed the key wicket of Bell, who made 55 from 220 balls with six fours.
It was a bruising defeat for England, who had enjoyed the better of the first day to reach 267-3. South Africa dominated from then, however, led by an epic 311 not out from Hashim Amla, an unbeaten 182 from Jacques Kallis and 131 from captain Graeme Smith to give them a daunting 637-2.
England began day four on 102-4, realistically needing to bat through at least two sessions to save the match, but poor shot selection contributed to their first defeat in a home test since Pakistan beat them at this venue in 2010.
Kevin Pietersen and Andrew Strauss had already gifted South Africa their wickets on Sunday with needlessly extravagant shots, and Ravi Bopara (22) followed suit just 30 minutes into the morning session. Bopara flashed at a delivery from Steyn that he could have ignored, dragging the ball onto middle stump.
Wicketkeeper AB de Villiers then dropped Bell, who was on 20, after he nicked a delivery from Tahir that he was trying to block.
Bell narrowly avoided being run out in the 62nd over when a direct hit from JP Duminy would have left him stranded by a foot, but he and Matt Prior otherwise batted with discipline to survive 90 minutes to the end of the session.
England whittled away South Africa's lead after lunch until Prior, having batted sensibly for 132 minutes, tried to sweep Tahir and was caught at slip by Jacques Kallis for 40.
The game appeared to be up for England when Steyn removed Bell with his second delivery with the new ball. Bell tried to open the face, but merely guided the ball to Kallis at slip.
Stuart Broad was caught behind for 0 off Steyn on referral and Graeme Swann launched a doomed counterattack and was caught for 7 by Alviro Petersen.
The victory was sealed when James Anderson was lbw to Tahir for 4. Anderson referred the call, but replays showed the ball would have clattered his stumps.
South Africa leads the three-match series 1-0 and will replace England at the top of the ICC world rankings it wins the second test, which starts next Thursday at Headingley.