In Benoni, Heather Knight's team amassed 202-4 from their 20 overs by taking advantage of some careless fielding and errant bowling.
Two-time dropped Danni Wyatt-Hodge became the first woman from England to reach 3,000 runs in T20 internationals with a brilliant 78 off just 45 balls.
With an undefeated 67 off 43 deliveries, Nat Sciver-Brunt maintained her excellent form and achieved her third consecutive T20 half-century.
Nadine de Klerk's 2-36 was the highlight of some otherwise depressing statistics, but all of South Africa's bowlers went for at least nine runs per over.
Sarah Glenn claimed 4-20, her third-best score in T20 internationals, as South Africa struggled to 168-6 in response.
Before a three-match, one-day international series and a one-off Test next month, England will try to clinch a series clean sweep in Saturday's last Twenty20 encounter in Centurion.
Brutal England wins easily.
In Saturday's first Twenty20 match in East London, England played well but not particularly well, although this was a completely resounding win.
Sarah Glenn claimed 4-20, her third-best score in T20 internationals, as South Africa struggled to 168-6 in response.
Before a three-match, one-day international series and a one-off Test next month, England will try to clinch a series clean sweep in Saturday's last Twenty20 encounter in Centurion.
Brutal England wins easily.
In Saturday's first Twenty20 match in East London, England played well but not particularly well, although this was a completely resounding win.
They got off to a bad start, falling behind 15-2 after Maia Bouchier chipped the ball to mid-wicket for 20. Two balls later, Sophia Dunkley made a duck with a nervy poke that glanced off the inside edge and onto the stumps.
Sciver-Brunt joined Wyatt-Hodge in the center as a result, and England never looked back.
They received assistance from South Africa, who dropped Sciver-Brunt on the 25 and Wyatt-Hodge twice, on the 9 and 29.
Sciver-Brunt joined Wyatt-Hodge in the center as a result, and England never looked back.
They received assistance from South Africa, who dropped Sciver-Brunt on the 25 and Wyatt-Hodge twice, on the 9 and 29.
Due to their line and length issues, the home team was unable to capitalize on a pitch that provided more bounce and speed than the stodgy East London surface.
That did not stop England's momentum, though, as they reached 200 for the fourth time in T20 internationals thanks to exciting cameos from Amy Jones (15 off seven) and Heather Knight (26 off 19).
In women's T20 internationals, only one team has ever tracked down a target of 200 or more, and it never seemed like it would happen here.
In the first over of South Africa's reply, Sciver-Brunt dismissed opener Tazmin Brits for a duck.
After putting up a fight with 30 off 24 balls, the returning Chloe Tryon became the fourth batter to be clean-bowled by Glenn, virtually guaranteeing England's triumph.
Reaction: "We want to strive for the 3-0 win now."
Heather Knight, captain of England: "I am quite happy with the team. Danni and Nat demonstrate their skills, which is what our batting squad is all about.
"We want to aim for the 3-0 victory."
"I concentrated only on taking wickets. I wanted to use the tempo and keep things simple because the pitch worked for me.
Laura Wolvaardt, captain of South Africa: "We did not have our finest overall performance. We did not take chances on the field, thus we allowed them to score too many runs with the bat.
"We had plans, but we got a bit carried away with the extra pitch bounce and went too short and wide."