Maritzburg had a challenge in front of them as they looked to retain their winning run in the Cup after beating Highlands Park in the previous stage at the same venue.
Meanwhile, the Clever Boys were looking to not only bag their second win after overcoming Free State Stars in the first round way in Bethelehem but keep their hopes of retaining their title alive.
Both sides started on a high and the encounter was a balanced affair when Haashim Domingo attempted a long range effort in the second minute, but he ballooned his effort over the bar.
However, coach Gavin Hunt was dealt a massive blow when he had to make a forced change when midfielder Thabang Monare had to be sacrificed for Keegan Ritchie in the 26th minute.
But the Students' efforts were eventually rewarded in the 37th minute when former Wits defender Nazeer Allie's interception beat his keeper Bongani Mpandle to hand the visitors the lead.
Right on the stroke half time, Buhle Mkhwanazi doubled the reigning champions' lead through a powerful header from Elias Pelembe's delivery from a corner kick.
The Team of Choice pushed for a goal to come back into the game, but Yannick Zakri was denied by goalkeeper Darren Keet, who was alert to collect the Ivorian's effort in the 59th minute.
Meanwhile, with 22 minutes to go, defender Robyn Johannes showed his class to deny Bandile Shandu as he attempted to pull one back for coach Fadlu Davids' troops.
Nonetheless, in the 70th minute Justice Figuareido, who replaced Bokang Tlhone managed to find the back of the net for the hosts as he beat Keet from close range.
The side from the KwaZulu-Natal midlands tried all they could for an equalier, but could not find away past the Students' solid defence manned by man of the match Johannes, and were knocked out of the tournament.