Fourteen teams participated in the 2005–06 Cypriot First Division.
The team with the most points at the end of the season crowned champions.
The teams had to declare their interest to participate in the 2006 UEFA Intertoto Cup before the end of the championship.
AEP Paphos, Alki Larnaca and Aris Limassol were relegated from previous season and played in the 2005–06 Cypriot Second Division.
They were replaced by the first three teams of the 2004–05 Cypriot Second Division, APOP Kinyras, APEP and THOI Lakatamia.