-scoreboard: England vs South Africa
Pietersen hit eight fours and a six in his 33-ball innings and Kieswetter slammed three fours and two sixes to accumulate 94 runs in 63 balls to help England post 168 after skipper Paul Collingwood elected to bat first.
In reply, only Graeme Smith (19), Jacques Kallis (11), JP Duminy (39) and Johan Botha (12) could manage double figures as South Africa collapsed to 129 in 19 overs.
Graeme Swann and Ryan Sidebottom scalped three wickets each, while Michael Yardy and Stuart Broad picked two scalps apiece to help England's cause.
Chasing 169 to win, South Africa found the going tough and lost half their side inside 10 overs at a score of 55 and if it wasn't for Duminy's 25-ball innings it could have been much more embarrassing for the Proteas.
Duminy added 37 runs with Mark Boucher (9) and shared 21 runs with Botha to provide some respectability to their runchase after the top-order crumbled.
Earlier electing to bat first, England lost opener Michael Lumb in the fifth ball when he was trapped in front of wicket by Johan Botha but they still went on to compile 65 runs in first six overs, courtesy Kieswetter and Pietersen's lusty hitting.
Kieswetter and Pietersen put the attack to the sword and shared as many as nine fours and a six in the first six over. Kieswetter started the proceeding with a blazing four at cover and Pietersen followed it up with two more fours in the second over of Dale Steyn.
Morne Morkel was at the receiving end in the next over when Pietersen slammed him at mid-wicket and then picked up another one in the last delivery.
There was still no respite for Morne as Peitersen shoveled a pull through square leg in his next over to pick up a four and then slammed one at mid-wicket.
Kieswetter then welcomed Charl Langeveldt with a six at long-off and went on to score two more fours to amass 16 runs off the over.
After a few silent over, Pietersen stepped the tempo once again in the 11th over, hammering Steyn for two fours and a six to accumulate 16 runs en route to his fifty.
However, Botha struck in the second ball of the next over to remove Pietersen. Looking to loft the ball over leg gully, his inside-out sweep landed straight in Graeme Smith's hands as England slipped to 98 for two in 11.2 overs.
Paul Collingwood then hit 14 runs in nine balls, which included two massive sixes, while Kieswetter also played some good shots but once they were gone England lost the momentum.
Kieswetter was holed out by Steyn, while Collingwood's miscued shot landed in wicketkeeper Mark Boucher's gloves.
Eoin Morgan (21), Tim Bresnan (13) and Michael Yardy (8) then did their bit to swell the England innings.
Johan Botha was pick of the bowlers as he bagged two wickets for 15 runs, while Jacques Kallis gave away 15 runs in his three overs to put break on the England innings.
Morne Morkel and Charl Langeveldt scalped two wickets apiece for 40 and 34 runs respectively but the most expensive bowler was Dale Steyn, who bleded 50 runs in his four overs.