Injury-plagued Green suffered what appeared an abdominal injury amid a brutal pace examination in rainy Potchefstroom, and Renshaw took a severe blow on his right wrist in the field, marring their 45-run (DLS Method) victory on Wednesday that prevented a series whitewash.
Green's planned return to bowling after a shoulder problem was shelved after a torrid over when a lightning Corbin Bosch beamer felled him, hitting him straight in his box, before he rose to hit the next delivery for six, but then got hurt again trying painfully to swat a bouncer.
After the match, captain Mitch Marsh reported: "Haven't spoken to them yet, but hopefully they're both OK."
With the first of the three Tests set for Durban in nine days' time, there are already concerns over whether Josh Inglis, who broke a finger in the first ODI, will be fit.
It spoiled a good-news day as Pat Cummins made an encouraging comeback and the rejuvenation of Adam Zampa and Alex Carey helped inspire Australia to a morale-boosting win.
The final day-nighter was eventually abandoned under the lights as a downpour ruined the denouement, but Australia were vastly improved after their capitulation in chases in the first two matches.
Half-centuries from Carey (74 off 88 balls) and captain Mitch Marsh (56 off 42), plus 48 from Ollie Peake, propelled Australia to 9-322 after they'd been sent in, with South Africa never threatening to pull off the highest successful ODI chase at the ground.
By the time the rain, which had delayed the start by half an hour, returned to spoil the fun, Australia were in control.
Zampa (2-34 off six overs) rediscovered his best after recent struggles and Xavier Bartlett earned a couple of key early wickets (2-25 off five) as only Ryan Rickelton (71no off 81 balls) looked a danger to the visitors, South Africa limping to 4-145 off 28 overs.
Cummins may have returned as bowler only and not captain, with Marsh completing his ODI stand-in job, but the official skipper's presence enthused everyone, with his 0-17 off five sharp, probing overs boding well for his leadership return in Durban.
"It didn't look like he hadn't played an ODI for 700 days. It was certainly nice having him back," Marsh said.
"Disappointing series, but nice to finish with a win. We came here to win this series, but there's some great lessons learned,"
Marsh himself couldn't be faulted, smashing his third straight fifty following 60 in Durban and 84 in Johannesburg.
Marsh and Travis Head (24 off 20) were electric again with a 78-run opening blitz at nine-an-over, but this time the middle order built much more assiduously against a Proteas side not helped by resting key spinner and player-of-the-series Keshav Maharaj, and captain Temba Bavuma among four changes.
It wasn't easy once Bjorn Fortuin trapped Marsh lbw and Gerald Coetzee bowled Cooper Connolly (23) with a brilliant yorker, but 20-year-old Peake impressed again with Carey as they put on 73 off 88 balls, the sort of partnership Marsh had been crying out for.
Peake must have thought he'd cracked a boundary off Bosch to take him to his landmark 50, only for Fortuin to take a dazzling diving catch behind point.
Renshaw (30) and Carey put on 66, with the keeper's drought-busting 88-ball knock ended by the formidable Bosch (4-60 off nine overs). It was Carey's first international half-century in 17 ODI and Test innings since his Ashes hundred in Adelaide last December.
Green's absence caused more problems for an already depleted bowling attack, with Nathan Ellis and Jack Edwards injured, but Bartlett's spell was superb and Zampa was back to his squeezing, probing white-ball best, having first-match centurion Matthew Breetzke stumped and trapping Tristan Stubbs lbw.
Next stop, Durban.
"The guys are excited, I know everyone is keen for the Test series," enthused Carey.
"We'll start the prep tomorrow."
