The hosts take an unassailable 2-0 lead in the series, with the third and final match to take place in Derby on Monday.
The Proteas posted 148-6 in their 20 overs after Anneke Bosch (61 off 57 balls) and Lara Goodall (42 off 34) put on 102 for the first wicket.
While No 3 batter Laura Wolvaardt chipped in with 21, England picked up wickets regularly in the final four overs of the innings to keep their opponents below 150.
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Katherine Brunt becomes England Women's highest ever wicket-taker!
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🏴 ENGvSA 🇿🇦 | @KBrunt26 pic.twitter.com/2nQY94IxHl
— England Cricket (@englandcricket) July 23, 2022
England reached their target with an over to spare.
Captain Nat Sciver top-scored with 47 off 41 balls, while Ayabonga Khaka, Masabata Klaas and Chloe Tryon all took a wicket for the visitors.
