Goals from Mandla Masango and Aubrey Modiba on either side of half-time saw a 10-man Matsatsantsa remain on course to defend their cup crown.
The hosts had an early opportunity to open the scoring after Ronwen Williams made a mess of an aerial ball in the third minute, but the keeper recovered to pull off a good save from close range.
The deadlock was finally broken in the 36th minute as Thuso Phala broke away down the flank before finding Masango inside the box, with the latter making no mistake to tap home from close range.
SuperSport took their advantage into the half-time break as they fended off the threat of conceding in the final minutes, with Denwin Farmer clearing his lines as KwaDukuza pushed for an equaliser.
Modiba scored late on to double the visitors lead as he finished off with a powerful effort.
There was drama late on as substitute Thabo Mnyamane was shown a straight red card just over 20 minutes after coming on for Masango.
Mnyamane will now miss his side's next two fixtures – both Absa Premiership clashes against Tshwane rivals Mamelodi Sundowns.
KwaDukuza United: Tsengwa, Mjoli, Mthabela, Aphane, S Mkhwanazi, B Khumalo, Ndlela (Madela 82'), Mseleku (Thwala 46'), Luthuli, Gatebe, Zondi
Subs not used: Nguse, Ndlovu, Buthelezi, Radebe, Mthembu
SuperSport United: Williams, Morton, Daniels, Farmer, Bhasera, Mokoena, Nel (Furman 77'), Modiba, Masango (Mnyamane 66'), Phala, Nkhatha (Brockie 46')
Subs not used: Pule, Mashamaite, Ritchie, Letsholonyane