Oldi Majtara put Zejtun ahead and Karl Sacco levelled matters early in the second half. However goals by Charlo Magro, Carmel Formosa and Adrian Carabott gave Zejtun the three points.
Mellieha suffered a heavy 0-3 defeat to Zebbug Rangers in another match on Saturday.
On Sunday, Rabat Ajax take on Naxxar Lions while St. Patrick face Senglea Athletic.