Masandawana got out of the starting blocks the quickest as good interplay between the forwards saw Themba Zwane get a shot away which was bravely blocked in the third minute.
Celtic retaliated with a chance of their own with the final shot coming from Victor Letsoalo's thunderous effort just brushing the upright in the sixth minute.
Sundowns applied the pressure as Celtic looked to catch them on the counter. Percy Tau got a shot away in the box that rattled the crossbar, saving the visitors' blushes with a 19 minutes gone on the clock.
Hlompo Kekana tried his luck from his own half, looking to catch Patrick Tignyemb off his line, but the Celtic goalkeeper managed to save the effort as the game reached the half hour mark still goalless.
Neither team managed to break the deadlock in the final 10 minutes of the half as Letsoalo squandered a golden chance by firing over the crossbar from 12-yards out on the stroke of halftime.
The hosts netted just after the restart as Thokozani Sekotlong rose highest and sent in a powerful header past Tignyemb to give Sundowns a 1-0 lead after 46 minutes of play.
Eight minutes later, Sundowns doubled their lead through a Tiyani Mabunda strike from the edge of the box as the Brazilians took a firm grip on the game.
Celtic replied in the 60th minute through an effort from Ronald Pfumbidzai after a great run through the middle as the full-back made it 2-1 with Celtic looking to get back into the game.
With 15 minutes remaining, Zwane played in Percy Tau and the diminutive striker finished clinically to make it 3-1 to Sundowns.
After great play by Sundowns, Zwane managed to get his name on the scoresheet as he made it 4-1 to his side with five minutes left to play.
That proved to be the final nail on the Celtic coffin as Sundowns claimed all three points.