According to the Amakhosi medical team, the 27-year-old fractured his ankle in the 3-0 win away to Stellenbosch FC over a week ago.
The medical team confirmed that Khuzwayo will undergo surgery on Friday.
“Brilliant will undergo surgery on Friday,” Amakhosi's physiotherapist Dave Milner said.
Khuzwayo was left out of the 18-man squad that traveled to Polokwane last weekend, with Luthando Sixhaso deputizing for first choice goalkeeper and captain Itumeleng Khune against Baroka.
With Khune set to feature for Bafana Bafana in the upcoming international friendlies against Guinea-Bissau and Angola, Chiefs would hope he comes back injury free.
Should anything happen to Khune, the Glamour Boys would face Sundowns without their two experienced goalkeepers - provided Khuzwayo is ruled out of the clash completely.
Sixhaso is yet to make his debut for the Soweto giants as he continues to gain as much experience as possible. He's considered as an understudy to both Khune and Khuzwayo.