Boland's double strike left the Proteas 2-20 when rain set in and eventually ended play before tea on Sunday (Monday AEDT) after Australia won the toss and went with four quicks.
His wickets came as just 74 balls were possible on day one, but again showed why the Victoria veteran is the perfect man for these conditions.
Boland 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.
Boland then briefly thought he had Temba Bavuma lbw for his second career hat-trick, but the Proteas' captain had edged the ball into his pad.
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 37-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.
For South Africa, the wet weather looms as a massive blow to their hopes of coming from 1-0 down to win the series.
More rain is forecast for the morning of day two and day four, before the series moves to Cape Town next week.
They have at least welcomed back pace spearhead Kagiso Rabada for this Test in place of spinner Keshav Maharaj, with fellow tweaker Simon Harmer holding his spot.
Marques Ackerman did well opening on debut after never doing so in first-class cricket, fighting through 32 tricky balls to be unbeaten on five when the rain hit.
Matthew Breetzke has also come into the side, with Tristan Stubbs and Kyle Verreynne axed.
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