Seamer Lungi Ngidi defended seven runs in the final over to bowl South Africa to an unlikely one-run victory as England folded at the death in the first Twenty20 International on Wednesday.
England needed seven from their final seven balls with five wickets remaining, but collapsed in the face of Ngidi's off-cutters on a slow wicket to add five runs for the loss of four wickets.
South Africa had posted 8-177 in their 20 overs, a record score in East London, but England were cruising when Jason Roy blasted 70 from 38 balls and captain Eoin Morgan an excellent 52 from 34.
The visitors lost their nerve at the finish, though, in what will be a tough lesson at the start of the build-up to the Twenty20 World Cup to be played in Australia in October.
Opener Roy provided the power at the top of the England order with superb straight hitting that included seven fours and three sixes.
He was out with England needing 46 from 34 balls and with seven wickets in hand, a simple enough equation on a docile pitch.
Their cause was strengthened when Morgan took up the mantle to take them to the brink of victory in the final over, but Ngidi (3-30) showed excellent skill and control to wrestle the game South Africa's way.
Having earlier picked up the key wicket of Ben Stokes (4), he removed Tom Curran (2) and Moeen Ali (5), before Adil Rashid (1) was run out on the last ball going for a second run that would have tied the game and led to a super over.
South Africa's score was boosted by Temba Bavuma's 43 from 27 balls, his runs coming in an unfamiliar opening position.