Jose Ali Meza and Andile Jali retained their spots in the Sundowns line-up, while Tebogo Langerman made a welcome return at left back. For the visitors, there was a debut for former Kaizer Chiefs and Sundowns defender Mario Booysen.
Bonginkosi Ntuli looked to give Usuthu the lead after two minutes, but the forward volleyed over the goal of Denis Onyango following a good build-up.
Sundowns though had the ball in the back of net five minutes later, but Themba Zwane was adjudged offside following a spate of passes.
After long spells of possession, the Brazilians finally broke the deadlock when Meza tapped in to an empty net following a through pass from Zwane.
Masandawana doubled their advantage 12 minutes from the break when Booysen headed into his own net after looking to clear Jali’s long cross.
Sundowns went further in front nine minutes later when Gaston Sirino sent Neil Boshoff the wrong way from the penalty spot after Thapelo Morena was brought down down in the area.
Sirino went on to grab his second and Sundowns' fourth goal 12 minutes from full-time with a first-time finish outside the area following good work by Zwane in the final third.
Mauricio Affonso came on for fellow South American Meza, as Masandawana instituted their first substitution in the final 20 minutes. Affonso joined the scoring party as he headed home the fifth four minutes to the end.
The Brazilians comfortably marched into the last eight along with Maritzburg United, Golden Arrows, Kaizer Chiefs, Orlando Pirates and SuperSport United.
Sundowns: Onyango, Langerman, Ngcongca, Madisha, Jali, Kekana, Lebusa, Sirino, Meza, Zwane, Morena.
Subs: Mweene, Vilakazi, Coetzee, Lakay, Maboe, Mahlambi, Affonso.
AmaZulu: Boshoff, Sikhakhane, M.Gumede, Xoki, Booysen, Vilakazi, Darpoh, Sithebe, Ncube, Karuru, Ntuli.
Subs: Mbatha, P. Gumede, Khumalo, Morton, Maduna, De Jong, Majoro.