Fourteen teams participated in the 1999–2000 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 2000 UEFA Intertoto Cup before the end of the championship.
Evagoras Paphos, Doxa Katokopia and Aris Limassol were relegated from previous season and played in the 1999–2000 Cypriot Second Division.
They were replaced by the first three teams of the 1998–99 Cypriot Second Division, Anagennisi Deryneia, Ethnikos Assia and APOP Paphos.