Debut goals from Thamsanqa Sangweni, Tebogo Langerman and Edward Manqele, added to another strike from Lebohang Mokoena, handed the Brazilians a record win over Amakhosi, who scored a consolation goal through Reneilwe Letsholonyane, and also missed a late penalty.
Sangweni got his Sundowns career to a dream start when he connected with an inswinging corner from Teko Modise in the seventh minute, and powered home under pressure from a group of Chiefs defenders.
Six minutes later it was another set-piece struggle for Chiefs as they failed to clear out a corner-kick, and Langerman powered home a low left-footed shot from inside the box.
Two minutes later Siyabonga Nkosi tried a long-range shot with his weaker left foot from 30 yards, but it went straight into the hands of Wayne Sandilands.
In the 24th minute it was 3-0 to the home side.
Modise swung the ball into the box and Manqele headed on target; Itumeleng Khune saved, only for Mokoena to tap home from the rebound.
If Chiefs fans thought it was all over they were wrong, as Sundowns had one more goal in them before the interval.
From a counter-attack the Brazilians caught the Chiefs defence off guard as Modise crossed from the left wing and found the unmarked Manqele, who headed home from close range to make it 4-0 in the 37th minute.
At first Chiefs showed no hunger to get back into the match in the second half, while Sundowns continued to search for goals.
In the 64th minute, however, Chiefs had a free-kick from 25 yards, but Sandilands made a good save to deny Bernard Parker.
In the 72nd minute Chiefs had another chance when Parker sent a ball into the box, but Sthembiso Ngcobo headed wide from six yards, after the keeper had come out and certainly looked beaten.
Four minutes later Chiefs got their consolation goal when Ngcobo brought the ball back into the box, Parker shot, and the deflected ball fell onto the path of Letsholonyane, who finished from six yards out to make it 4-1.
There was drama late on when Chiefs earned a penalty in the 86th minute, after debutant defender Wayne Arendse was adjudged to have handled the ball in the box.
Josta Dladla stepped up but to take the penalty but his shot hit the post, and despite eight minutes of added time Chiefs chould not add to their tally.
The Brazilians join Orlando Pirates, SuperSport United and Moroka Swallows in the semi-final draw on Monday morning.
Mamelodi Sundowns (4) 4 (Sangweni 7, Langerman 12, Mokoena 24, Manqele 37)
Kaizer Chiefs (0) 1 (Letsholonyane 76)
Sundowns: W Sandilands, D Mampuru, P Masenamela, A Mabaso, M Mwanjale (W Arendse 40), T Sangweni, H Kekana, T Modise, T Langerman (E Rogers 82), E Manqele (Mushekwi 60), L Mokoena
Chiefs: I Khune, S Gaxa (Zvayisa 9), M Gould, E Mathoho, J Jambo, R Letsholonyane, S Nkosi, J Dladla, A Nale (Ngcobo 55), B Parker, L Majoro