Tristan Stubbs hit 72 off 28 balls as the Proteas suffered a 41-run defeat by England in the first T20I in Bristol on Wednesday.
Needing an improbable 235 to win, South Africa lost Quinton de Kock (two) and Rilee Rossouw (four) early on in their run chase.
Under-pressure opener Reeza Hendricks went on to make 57 off 33 balls and his dismissal in the 10th over brought Stubbs to the crease.
Having not batted in his first two T20I appearances in India, Stubbs made his first international innings count, smashing eight sixes and two fours to keep his team in the game.
But South Africa’s slim hopes of victory evaporated when Stubbs was caught off the first ball of the 19th over.
Earlier, Jonny Bairstow scored 90 off 53 balls as England posted a massive 234-6 – their second-highest T20I total.
Bairstow – who was dropped four times – hit three fours and eight sixes in a knock that finally ended when he was caught off the fifth ball of the last over.
Dawid Malan made 43 off 23 balls and Moeen Ali 52 off 18.
Lungi Ngidi took a career-best 5-39 for the Proteas, while Andile Phehlukwayo (63 runs in four overs) and Tabraiz Shamsi (49 in three) took a pounding.
Phehlukwayo was smashed for 33 in his fourth over, which included five sixes.
“They demolished us in the last 10 overs but we dropped four or five catches which cost us massively in the field,” said stand-in Proteas captain David Miller after the match.
“It was a phenomenal knock by Stubbsy, an extremely disappointing result but there are another two matches to get it right.”