It was England's first Test win since beating Australia in January 2014 and the third biggest win (by runs) in women's Test cricket.
Eighteen wickets fell on the third day with South Africa's nine falling in less than 20 overs as they were dismissed for 64, their lowest Test score (No.11 Ayanda Hlubi was unable to bat due to injury).
Test debutant Lauren Bell took 4- 27 to finish with match figures of 8-76 as the Proteas capitulated in pursuit of an unlikely world-record target of 351.
England captain Heather Knight set up the victory with 90 in the tourists' second-innings 236.
Nonkululeko Mlaba finished with six for 67 to become the first South African to take 10 wickets in a women's Test.
"It's really pleasing, we really put the graft in the last couple of days," said Knight. "There are only three of us in the squad who have been involved in a Test win before - we've had a lot of tough fought draws and a couple of losses."
"Very disappointing. I think we played a lot of good cricket in that Test match but let it slip in the last hour or two," said he counterpart Laura Wolvaardt. "We'll learn from this experience and hopefully the next [Test] will be better. The only way we can learn is by playing it. There is only so much you can learn in the nets beforehand."
Resuming on 1-31 England had their sights set on a much bigger target but, Knight aside, nobody was able to make the most of promising starts.
Nat Sciver-Brunt became the first of Mlaba's victims when she played on for 37 after a third-wicket stand of 67 with Knight.
Danni Wyatt-Hodge (23) and Amy Jones (24) brought quick runs in support of Knight but fell either side of lunch.
Sophie Ecclestone was trapped leg before by Mlaba, who then accounted for Knight in similar fashion.
The left-arm spinner bowled Ryana MacDonald-Gay and Nadine de Klerk removed Lauren Flier.
Faced with a tricky 20 minutes spell before tea South Africa lost Wolvaardt and Anneke Bosch cheaply.
When play resumed there was controversy over the dismissal of Annerie Dercksen as she was adjudged to have been caught at bat-pad by Tammy Beaumont off the bowling of Bell.
Dercksen stood her ground but was given out following a referral to the third umpire, leaving them 3-22.
While the decision looked correct South Africa were unhappy at the way it was reached as the decision review system (DRS) is not in place for the match due to the cost, though it was for the white-ball matches. Thus Wolvaardt was unable to overturn an lbw decision in the first innings when she appeared to have hit the ball.
Marizanne Kapp subsequently resisted with 21 but few others did as South Africa slipped to 6-33, then 8-44.
Mlaba hit three boundaries in a late flurry but her run out - one of two in the innings - after failing to ground her bat brought a shoddy end to a poor team effort.
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