Thabiso Hlalele and Myron Shongwe scored for Lidoda Duvha, in a game of two halves.
Matsatsantsa dominated from the offset, but were woeful in front of goal, with Katlego Mashego the main culprit.
Leopards took the lead against the run of play in the 41st minute when Hlalele latched onto a good through-ball by Walter Ramulondi before slotting home with a low shot.
Leopards continued their dominance in the second half and doubled their lead in the 59th minute when Robert Ng’ambi put Shongwe through on goal and the striker made no mistake as he slotted the ball past onrushing Supersport keeper Andre Arendse.
The visitors pushed more men forward in a bid to penetrate the Leopards defence, but the hosts were in defending the lead, eventually securing the points.