Boland's double strike left the Proteas 2-20 when rain set in before tea on day one of the second Test on Sunday, after Australia won the toss and went with four quicks at St George's Park
His wickets came as just 12.2 overs were possible across the opening five hours, but again showed why Boland is the perfect man for these conditions.
The Victorian first nipped a ball back off the seam to catch Aiden Markram's edge and remove his middle stump, bowling the opener for 11.
The next ball then pitched in almost the same spot, but this time went away off the wobble seam and took David Bedingham's edge on the way through.
It came after Lyon was left out of a red-ball Test when fit for the first time in 13 years, with Australia now clearly more open to going without a frontline spinner.
The 38-year-old has been overlooked twice when fit for pink-ball encounters in the past 18 months, but had played every daytime Test for Australia since July 2013 before Sunday.
Lyon has also now missed five of the past 10 Tests for Australia through a combination of injury and selection, and bowled just two overs in Perth last summer.
The tweaker had admitted he was "filthy" when left out of Australia's team against England for the day-night Test at the Gabba last year, keen to carry the legacy of spinners forward.
But with a green wicket at St George's Park and heavy clouds overhead, the veteran became dispensable.
"It's partly conditions, and Scotty Boland has been incredible whenever he's played Test cricket," captain Pat Cummins said at the toss.
"So it felt like it aligned this week and it was the right time to insert him.
"When there's anything in the wicket, he gets a lot of seam movement. He's super accurate, and even if it does flatten out he brings that control."
The signs Lyon wasn't playing were there on Sunday morning when he picked up a football during warm up, and appeared to congratulate Boland for his selection.
Australia also have the advantage of Matt Renshaw's off spin after his two wickets in the first Test win, along with Travis Head's tweakers and Beau Webster's ability to bowl off-breaks.
Lyon's omission was the only change for Australia, with Nic Maddinson to remain at the top of the order and Renshaw No.5 after his first Test heroics.
South Africa welcomed back pace spearhead Kagiso Rabada in place of spinner Keshav Maharaj, with fellow tweaker Simon Harmer holding his spot.
Marques Ackerman has done well opening on debut, fighting through 32 tricky balls to be unbeaten on five when the rain again hit.
Matthew Breetzke has also come into the side with Tristan Stubbs and Kyle Verreynne axed.
More rain is forecast across the opening two days of the Test, although the heaviest is predicted overnight.
A win at St George's Park will wrap up the series for Australia after their 214-run victory at Kingsmead Stadium last week, with the third Test in Cape Town next week.