| Competition: | Alpha Ethniki |
| Season: | 1980–81 |
| Winners: | Olympiacos 22nd Greek title |
| Relegated: | Panachaiki Atromitos |
| Continentalcup1: | European Cup |
| Continentalcup1 Qualifiers: | Olympiacos |
| Continentalcup2: | UEFA Cup |
| Continentalcup2 Qualifiers: | Aris Panathinaikos |
| Continentalcup3: | Cup Winners' Cup |
| Continentalcup3 Qualifiers: | PAOK |
| League Topscorer: | Dinos Kouis (21 goals) |
| Matches: | 306 |
| Total Goals: | 709 |
| Prevseason: | 1979–80 |
| Nextseason: | 1981–82 |
The 1980–81 Alpha Ethniki was the 45th season of the highest football league of Greece. The season began on 7 September 1980 and ended on 14 June 1981. Olympiacos won their second consecutive and 22nd Greek title.
The point system was: Win: 2 points - Draw: 1 point.
| Rank | Player | Club | Goals |
|---|---|---|---|
| 1 | Dinos Kouis | Aris | 21 |
| 2 | Grigoris Charalampidis | Doxa Drama | 15 |
| 3 | Thomas Liolios | Kastoria | 13 |
| 4 | Giannis Dintsikos | Kastoria | 12 |
| Dušan Bajević | AEK Athens | ||
| Kostas Charalampidis | AEL | ||
| 7 | Takis Papadimitriou | Panionios | 11 |
| Giorgos Togias | Korinthos | ||
| 9 | Giorgos Ananiadis | PAS Giannina | 10 |
| Maik Galakos | Olympiacos | ||
| Spyros Livathinos | Panionios | ||
| Dimitris Seitaridis | Ethnikos Piraeus |