AmaZulu FC will travel to the Mbombela Stadium where they will face TS Galaxy in the DStv Premiership match on Wednesday.
Kick-off is at 19h30 CAT.
Usuthu opened their campaign with a 1-1 draw at home to Orlando Pirates on October 24.
They fought back from a goal down to salvage a share of the spoils, thanks to a goal from striker Lehlohonolo Majoro.
AmaZulu took just 13 points from their 15 away matches in 2019/20, season.
The KwaZulu-Natal giants recorded wins at Baroka FC, Bloemfontein Celtic and Kaizer Chiefs.
Meanwhile, Galaxy’s first top-flight league match saw them record a 1-1 draw away to Tshakhuma Tsha Madzivhandila on October 25.
The Rockets’ goal was scored by veteran defender Bevan Fransman on the stroke of half time.
Galaxy struggled at home through the 2019/20 GladAfrica Championship (National First Division) season.
They claimed just three wins and 17 points from their 15 games as hosts.
In head-to-head stats, this will be the first top-flight league match between TS Galaxy and AmaZulu.