The touring side threatened to claim their first win against England in the format, having reached 77-1 in the 14th over while chasing a target of 127, but they instead lost four wickets in 16 balls to finish on 118-6.
Winfield, 24, hit a powerful 74 from 60 balls in England’s 126-6 after the early departure of captain Charlotte Edwards, whose unbeaten innings underpinned previous victories at Chelmsford and Northampton.
From that setback in the third over, Winfield took responsibility as she raced past her previous best of 36, driving powerfully and steering balls confidently through the leg side, including a six over mid-wicket off Chloe Tryon’s first ball to add to her nine fours.
It was the wrist-spin of Dane van Niekerk, making her 38th international T20 appearance aged only 21, who brought order to proceedings. A big-turning leg-break beat Natalie Sciver and Trisha Chetty reacted smartly to complete the stumping.
South Africa had won the toss on a good pitch and the early wicket of Edwards to a leading edge after scores of 62 and 75 hitherto provided the start they wanted.
Winfield responded by hitting Marizanne Kapp for three fours in a row, only for the highly-rated Sarah Taylor to drive to long off.
England were slightly off line with the new ball and Van Niekerk and Chetty put on 59 for the first wicket before confusion resulted in the run-out of Van Niekerk as Winfield held her nerve with time to throw.
Nerves may have got to the South Africans after the loss of Lizelle Lee to the accurate medium pace of Jenny Gunn.
Lydia Greenway and Sciver combined to run out Chetty and a brilliant overhead catch by Greenway at deep mid-wicket accounted for Mignon du Preez next ball.
The quick hands of wicketkeeper Taylor ran out Kapp and stumped Bernadine Bezuidenhout as the required rate reached 10 per over before the experienced Gunn held her nerve to keep a full length with the last six balls, allowing only four singles.
England captain Edwards said: “South Africa bowled and fielded well, but our experience counted in the end.
“Jenny Gunn bowled a brilliant last over, and I am really pleased with the way Lauren Whitfield went out and played so well at the top of the order. The future looks bright for us and there is a big two years ahead.”