Bongani Ndulula bagged a brace while Goodman Dlamini and Thokozani Mshengu were also on target to seal a convincing win.
Usuthu opened the scoring from the penalty spot in the fourth minute when Ndulula fired past Posnett Omony after he had been brought down by Moses Kwena just inside the box.
Goodman Dlamini doubled the lead two minutes later, firing home from just inside the box after a good cross from Luyanda Hlongwa on the right.
Willem Mwedihanga could have extended the advantage in the eighth minute but the lanky defender headed Njabulo Manqana’s corner over the crossbar at the far post.
Usuthu then created two more great chances midway through the first half with Hlongwa striking the crossbar in the 19th minute, while Rhamson Zhuwawo fired over the target from inside the box a minute later.
Leopards were reduced to 10 men on 32 minutes, when Djunga Munganga was given his marching orders for a foul on Stanley Kgatla.
Ndulula grabbed his second goal of the match on the stroke of half-time, firing a first time shot into the back of the net from the centre of the penalty area after he was set up by Mshengu.
Usuthu continued from where they left off after the break, with Goodman Dlamini forcing a great save from Omony in the 52nd minute after he was released by Mshengu on the left.
Ayanda Dlamini came on to replace Ndulula in the 65th minute and almost announced his arrival with a goal three minutes later, but was denied by Omony on two occasions.
The Nongoma-born forward was back in the thick of things again in the 81st minute but this time he saw his effort cleared off the line, after doing well to lose his marker and the goalkeeper.
However, the rout was completed a minute later when Mshengu beat Omony at the near post with a solid strike from the edge of the box.