Matt Derbyshire had put Omonia into a ninth-minute lead when he met Renato Margaca’s cross with a good header but the lead was cancelled out by Stathis Aloneftis thirty minutes later as he pounced on the Costas Panagi’s parry from a Giannis Gianniotas strike.
George Efrem won a penalty – which was contested by the Omonia players and bench – which brought about a 12 minute stoppage as angry Omonia fans threw fireworks onto the pitch.
Pieros Sotiriou tucked away the penalty.
Derbyshire thought he had equalised shortly afterwards but his goal was wrongly ruled out for offside.
Substitute Vander added a third in stoppage time.
The defeat was a double-blow for Omonia who saw their most hated rivals celebrate yet another league title triumph – a record equalling consecutive fifth – but also saw Akis Ioakim’s miss out on European football for the first time in 15 years.
Their misery was compounded by the sending off of Nicandro Breeveld and Ioakim – who was sent to the stands by referee Vasilis Demetriou.
Thomas Christiansen’s APOEL will start their Champions League campaign in the third qualifying round this summer.
In the other game, AEK Larnaca could only draw 1-1 with AEL – with the Limassol club booking their place in the Europa League qualifiers this summer instead of Omonia.
APOEL are in the Cyprus Coca-Cola Cup final where they will be seeking to clinch the double against fellow finalists Apollon.