A heavily-strapped Morne Morkel made two breakthroughs as South Africa pushed for victory on the fourth day of the fourth Test against Australia at the Wanderers Stadium on Monday.
Australia, set an impossible 612 to win, were 88 for three when bad light ended play.
With all three of South Africa's fast bowlers carrying injuries, it was Morkel, with what had seemed the most significant injury, who made the biggest impact.
The tall Morkel, playing in his last Test, dismissed both opening batsmen in an impressive eight-over spell despite heavy strapping around his midriff.
What was initially thought to be a probable match-ending side strain had been downgraded to an abdominal strain.
"He should bowl like that more often," quipped batsman Dean Elgar of Morkel's display of tight control at close to his best pace.
"We've had quite a few bowlers who have pulled up with niggles.
"It was a concern for us if they were going to bowl in the second innings. Thank goodness they could get through quite a few overs for us and bowl quite well on a wicket which is actually assisting them quite nicely."
Morkel came on to bowl as second change and with his tenth ball trapped Matt Renshaw leg before wicket with a full-length delivery angled in to the left-hander.
Left-arm spinner Keshav Maharaj also won a leg before decision, when Usman Khawaja played no shot to a ball which spun sharply out of the rough, before Morkel struck again when Joe Burns played across a ball of almost yorker length.
Burns, one of three replacements for the Australian trio banned for their role in a ball-tampering scandal, made 42 off 84 balls with five fours and a six.
South Africa's other fast bowlers, Kagiso Rabada and Vernon Philander, were struggling with a stiff lower back and a groin strain respectively. They both bowled short spells with the new ball without success.
"If we've got them running in at 60 percent it's going to be awesome for us for tomorrow," said Elgar.
Captain Faf du Plessis hit 120 and Elgar made 81 before South Africa declared at 344 for six. They shared a fourth-wicket partnership of 170, the best for any wicket by either side during the series.
Elgar admitted to some sympathy for the Australians after a week marred by the ball-tampering scandal which resulted in former captain Steve Smith, David Warner and Cameron Bancroft being sent home and banned.
"It's a combination of us playing good cricket and maybe a bit of a weary Australian side," said Elgar. "They've been through quite a lot in the last two weeks. They should be a bit tired."
With South Africa leading the series 2-1, their batting effort made sure they would secure their first home series win against Australia since 1969/70, whether or not their bowling options were limited.
It also left Australia with nothing to play for but pride after a turbulent tour.
"We're probably not chasing 550 in a day," admitted Burns.
"We'd take a draw tomorrow. It's been a very tough week for the Australian cricket team. Tomorrow is about coming out and trying to put in a good performance for Australia, trying to do your country proud."
Du Plessis made his first major contribution of the series after scoring only 55 runs in his first seven innings.
When he was on 43, he needed lengthy treatment after a ball from Pat Cummins split open the right index finger he broke earlier in the season.
But he went on to make his eighth Test century and his third against Australia. He faced 178 balls in his innings, which included 18 fours and two sixes.
Cummins was again Australia's best bowler, taking four for 58. His match figures of nine for 141 were the best of his career.
221 and 88 for 3 (Handscomb 23*, Shaun Marsh 7*) need 524 more runs to beat South Africa
488 and 344 for 6 (du Plessis 120, Elgar 81)