Jonny Bairstow helped to spare the embarrassment, but there proved no way back into the match after England crashed to 20 for six in the first five overs - the worst ever start to a one-day worldwide fixture.
'To win or lose on the toss in a major tournament is hard to take, and makes it one-sided, which I don't think is good for anyone'.
Bairstow (51) shared half-century stands with David Willey and then debutant Toby Roland-Jones, but too much damage had already been done when England, put in under cloud cover, came badly unstuck against Kagiso Rabada (four for 39) and Wayne Parnell (three for 43). But it was a reminder that, when the ball moves, England remain a little vulnerable.
Hashim Amla was the leading run-scorer for the Proteas with 152 including two fifties and a top score of 73.
That was the end of the foyrth over and next ball Alex Hales, trying to drive Rabada, got an outside edge to Amla and England were 15 for four. It was a dramatic turn of form at Lord's, after England had posted over 300 runs at Headingley and Southampton to win the first two internationals.
Amla became Roland-Jones' first global scalp in the 16th over but any thought of a Proteas slump was quickly ended by JP Duminy and AB de Villiers - the pair seeing South Africa home with plenty of time to spare. Best of them all arguably was Faf du Plessis' head-high take at second slip to account for Jos Buttler. In the seventh over of third ODI, he reached the landmark of 7000 runs. Because of the failure in the last two games.
But Roland-Jones bagged a maiden worldwide wicket when Amla dragged a pull on to his stumps to end an opening stand of 95.
Eoin Morgan, the England captain, fell for eight on his Middlesex home ground when another swinging Parnell delivery took the outside edge this time to give wicket-keeper Quinton de Kock an easy catch.
Even so, England's untimely trouncing was merely delayed a little.