It began on 20 December 1980 with the preliminary round and concluded on 27 June 1981 with the replay final which was held at Tsirion Stadium.
Omonia won their 5th Cypriot Cup trophy after beating Enosis Neon Paralimni 3–0 in the final.
In all rounds each tie was played as a single leg and was held at the home ground of one of the two teams, according to the draw results.
If extra time was drawn, there was a replay at the ground of the team who were away for the first game.
14 clubs from the Cypriot First Division and the rest clubs from the Cypriot Second Division met the winners of the preliminary round ties: Because the match ended in a draw after the extra time, a replay match was played.