First-choice keeper Khune is due to undergo knee surgery, prompting an opportunity for Kaizer Chiefs teammate Khuzwayo.
Khuzwayo has only played once this season, picking up a man-of-the-match award in Chiefs' Soweto Derby victory over Orlando Pirates on the weekend.
The 25-year-old joins Jackson Mabokgwane and Ronwen Williams as the shot-stoppers in the Bafana camp.
Mabokgwane has also seen limited game-time at Mpumalanga Black Aces this season, as he shares the keeping duties with Shu-Aib Walters. Mabokgwane has made four League apperances for AmaZayoni in 2015/16.
Williams has been an ever-present feature for SuperSport United, starting all 14 of their matches in all competitions.
Keepers that can feel aggrieved to be overlooked for selection, include Belgium-based Darren Keet, who has kept seven clean sheets in 15 games for Kortrijk, and Moeneeb Josephs, who has helped Bidvest Wits to the top of the Absa Premiership standings.
Bafana will visit the Sable Antelopes on Friday afternoon before hosting the return duel at Moses Mabhida Stadium in Durban on November 17.