A superb second-half comeback saw the Cypriots record their first ever victory in the Champions League group stages
Both teams had chances to open the scoring in the first half, but the game's first goal didn't arrive until the second half, and it was Zenit who struck first.
Danny ran freely through a short-staffed APOEL defense before sending a perfectly weighted pass to Konstantin Zyryanov, who made no mistake with a crisp finish in the 63rd minute to put the visitors in front.
The hosts levelled matters 10 minutes later when a scuffed Helio Pinto shot fell to Jorge Manduca, who made no mistake with his emphatic finish.
Moments later the comeback was complete when Ailton finished past Malafeev with a composed right-footed strike from just inside the box.
The nightmare continued for Zenit when Bruno Alves received his marching orders for a second yellow card following a cynical challenge on Ailton as the Brazilian forward looked to run free of the Zenit backline.
Viktor Fayzulin struck the post with seconds remaining as the 10-man Russians pushed for an equalizer but in the end the Cypriots were able to hold on for a famous victory.