An unbeaten stand from England openers Matt Prior and Ian Bell gave England a ten wicket victory with 35 overs to spare at Trent Bridge.
Stuart Broad recorded his best ever international figures as England made an explosive start with the ball and never relinquished their grip of the game.
Andrew Flintoff smashed Dale Steyn's middle stump to remove the visitors for 83 after just 23 overs and Broad's haul included four wickets in 16 balls.
South Africa won the toss and elected to bat but their top order struggled to find the middle of the bat and found England wicket keeper Matt Prior in sparkling form.
"The performance was spectacular and we hammered them convincingly," said England captain Kevin Pietersen.
"Matt Prior was outstanding and what's important now is that he produces that form game after game.
"We've got four bowlers hitting ninety miles per hour and it's really working for us."
Matt Prior took routine catches off Broad's bowling to dismiss Herschelle Gibbs, JP Duminy and Andre Botha and dived across first slip to take a fine catch to end Graeme Smith's innings.
Flintoff kept the pressure on the tourists with a solid spell that saw AB De Villiers fall lbw and Mark Boucher caught behind.
Steve Harmison entered the attack and made an immediate impact with two wickets in his first over. Andre Nel lofted the ball to Luke Wright at mid-wicket and Albie Morkel was caught behind.
England: Ian Bell, Matt Prior (wk), Owais Shah, Kevin Pietersen (capt), Andrew Flintoff, Paul Collingwood, Samit Patel, Luke Wright, Stuart Broad, Steve Harmison, James Anderson
South Africa: Graeme Smith (capt), Herschelle Gibbs, Jacques Kallis, AB de Villiers, JP Duminy, Mark Boucher (wk), Albie Morkel, Johan Botha, Andre Nel, Dale Steyn, Makhaya Ntini