Preparing for the Optus Stadium match in Perth on Sunday night, Canham trained fully on Friday but pulled up sore and is now in danger of missing the upcoming Bledisloe Cup series against the All Blacks.
Coach Les Kiss has reshuffled his starting line-up with Lukhan Salakaia-Loto coming into the starting side with Lachlan Shaw added to the bench, while Jeremy Williams will take over the line-out calling duties.
Wallabies skipper Harry Wilson said it was disappointing to lose Canham, who has established himself as the premier lock in the Australian pack.
"It's always a big loss when you lose your line-out caller and someone like Canham, who's been playing some really good footy for us," Wilson said on Saturday morning.
"But with someone like Jeremy Williams, he has called international footy before and really looking forward to him having that opportunity, and then someone like Lukhan Salakaia-Loto coming into the starting team.
"I know how excited he is and he's been raring to go and he might not offer Canham's jumping ability but, gee whiz, he can offer some other stuff around the field."
Wilson said Queensland firebrand would bring some valuable physicality to the clash with the abrasive Springboks.
"We know they're a team that will want to go through us and they're a big abrasive forward pack so to have someone like Lukhan next to you, it gives you a bit of confidence, and he really relishes those sort of battles, when he's up against Franco Mostert and Eben Etzebeth.
"He loves pulling the gold jersey and to get an opportunity to go against the best in the world, it's exciting for him."
Last year Wilson sparked a miracle fightback from 22-0, scoring two tries to lead Australia to a stunning 38-22 victory, the Wallabies' first win at Ellis Park in 62 years.
The No.8 said while the result gave his team belief heading into the battle against the top-ranked side, they would need to be in the fight from the opening whistle.
"We'll definitely look back on some of the things we did really well against them, and it definitely gives the boys a lot of confidence, but I guess we're really aware that it means nothing tomorrow night," Wilson said.
"We know what sort of team they're going to be - we've watched them very closely in the last four matches against the Kiwis and some unbelievable Test footy and now we get the opportunity to go against them.
 "Obviously there's been a few changes, but they've still got 10 World Cup winners in there."
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