The hosts scored seven tries, converted six of them and added a penalty goal, while the Irish province replied through five converted tries in a display that left the attack coaches smiling.
The Cell C Sharks enjoyed a half-time lead of 17-14 through converted tries by Springboks Jaden Hendrikse and Eben Etzebeth to add to a Curwin Bosch penalty goal, but they cut loose with five more tries in the second stanza to take the game away from Munster.
Springbok hooker Bongi Mbonambi led the charge with two off the back of their powerful driving maul, while speedster Werner Kok, Bosch and the prolific Makazole Mapimpi also crossed. Bosch finished with a personal tally of 20 points.
Munster replied with first-half tries through Shane Daly and Dave Kilcoyne, but their second-half efforts from Diarmuid Barron, Mike Haley and Fineen Wycherley were merely consolations as the home side celebrated a well-deserved win in front of a delighted crowd.
The Cell C Sharks will play the winner of Sunday's round of 16 match between Stade Toulousain and Vodacom Bulls in the quarter-finals.
It was an exhilarating first half in this contest in the bright Durban sun. The opening stanza produced some high-quality rugby between the South African and Irish sides. With all the tries converted at that stage, it was Bosch’s early penalty goal that proved to be the difference between them at the halfway stage.
The second half got off to a cracking start when Mbonambi scored twice within three minutes to show their intent, with Kok adding a third a few minutes later.
Mapimpi had a good game, and he was instrumental in several attacking plays. He sent Kok away for his try and was later alert to scoop up a loose ball and race through for his five-pointer.
In-between Bosch also showed his pace and determination to score when he raced down the touchline after another defensive lapse from the visitors, who refused to give up in the punishing Durban heat and humidity for a couple of consolation tries.
Cell C Sharks 50 (17) - Tries: Jaden Hendrikse, Eben Etzebeth, Bongi Mbonambi (2), Werner Kok, Curwin Bosch, Makazole Mapimpi. Conversions: Curwin Bosch (6). Penalty goal: Bosch.
Munster 35 (14) - Tries: Shane Daley, Dave Kilcoyne, Diarmuid Barron, Mike Haley, Fineen Wycherley. Conversions: Jack Crowley (5).