A La Liga 1980–1981-es szezonja volt a bajnokság jubileumi, 50. kiírása. A bajnokságban 18 csapat vett részt, a szezon 1980. szeptember 6-án rajtolt, és 1981. április 26-án ért véget. A győztes a Real Sociedad lett, ez volt a klub első bajnoki címe.
| | ALM | ATH | ATM | BAR | BET | ESP | HÉR | LPA | MUR | OSA | RMA | RSO | SAL | SEV | SPG | VAL | VLD | ZAR |
| AD Almería | | 1-1 | 2-1 | 2-5 | 0-2 | 2-0 | 0-3 | 0-1 | 0-0 | 1-1 | 1-2 | 3-2 | 3-2 | 0-0 | 1-1 | 1-0 | 1-1 | 3-1 |
| Athletic Club | 5-1 | | 3-1 | 4-1 | 2-0 | 1-2 | 5-3 | 1-3 | 3-0 | 1-1 | 1-1 | 0-2 | 6-1 | 3-0 | 1-1 | 4-0 | 4-1 | 0-1 |
| Atlético de Madrid | 2-1 | 2-1 | | 1-0 | 0-4 | 1-0 | 1-0 | 2-2 | 2-1 | 0-0 | 3-1 | 2-0 | 1-1 | 2-0 | 0-0 | 3-1 | 5-2 | 1-2 |
| FC Barcelona | 6-0 | 0-1 | 4-2 | | 1-3 | 3-1 | 6-0 | 1-0 | 1-0 | 6-0 | 2-1 | 2-0 | 3-0 | 3-1 | 3-1 | 0-3 | 2-1 | 0-0 |
| Betis | 2-0 | 2-0 | 0-1 | 1-1 | | 1-2 | 2-0 | 4-1 | 1-0 | 1-1 | 1-1 | 1-0 | 5-0 | 2-0 | 2-0 | 1-1 | 2-2 | 2-0 |
| RCD Español | 1-0 | 1-0 | 2-0 | 1-0 | 1-2 | | 2-1 | 3-1 | 2-1 | 0-0 | 2-1 | 0-0 | 2-1 | 2-2 | 1-0 | 1-2 | 0-0 | 1-1 |
| Hércules CF | 1-0 | 1-2 | 1-2 | 0-1 | 0-1 | 2-0 | | 2-3 | 1-0 | 0-0 | 1-2 | 2-0 | 3-2 | 5-1 | 1-1 | 1-1 | 1-1 | 1-1 |
| UD Las Palmas | 3-0 | 1-3 | 1-1 | 1-4 | 2-4 | 2-0 | 1-1 | | 1-2 | 2-0 | 1-0 | 0-3 | 1-1 | 1-2 | 3-1 | 1-4 | 0-2 | 3-0 |
| Murcia | 2-1 | 5-4 | 0-2 | 1-2 | 2-0 | 1-1 | 2-2 | 1-2 | | 1-0 | 1-1 | 0-2 | 1-1 | 0-0 | 2-1 | 0-2 | 0-0 | 0-1 |
| Osasuna | 2-1 | 2-0 | 0-0 | 1-0 | 1-2 | 1-0 | 1-2 | 1-0 | 3-1 | | 1-2 | 0-3 | 1-1 | 2-1 | 3-0 | 2-0 | 2-0 | 1-0 |
| Real Madrid | 4-0 | 7-1 | 2-0 | 3-0 | 4-2 | 1-2 | 3-0 | 3-0 | 4-0 | 3-1 | | 1-0 | 2-0 | 3-2 | 1-0 | 2-1 | 1-1 | 2-0 |
| Real Sociedad | 3-1 | 4-1 | 2-2 | 2-0 | 2-2 | 2-1 | 1-1 | 2-0 | 1-0 | 2-1 | 3-1 | | 1-0 | 3-0 | 1-2 | 2-1 | 1-0 | 1-0 |
| UD Salamanca | 3-2 | 2-1 | 1-1 | 2-1 | 2-0 | 3-2 | 0-1 | 0-2 | 0-3 | 1-2 | 1-3 | 0-2 | | 0-0 | 2-2 | 0-1 | 2-1 | 3-1 |
| Sevilla FC | 1-0 | 2-0 | 1-1 | 1-1 | 2-1 | 2-0 | 0-0 | 3-2 | 1-0 | 1-0 | 2-0 | 0-0 | 1-0 | | 3-2 | 1-0 | 1-0 | 0-0 |
| Sporting de Gijón | 5-2 | 1-1 | 3-0 | 2-1 | 2-0 | 0-1 | 3-1 | 2-1 | 2-0 | 5-1 | 4-0 | 2-2 | 4-0 | 3-0 | | 0-0 | 4-1 | 1-1 |
| Valencia CF | 3-1 | 0-0 | 1-1 | 3-3 | 3-1 | 3-1 | 0-2 | 3-1 | 3-2 | 4-1 | 2-1 | 3-2 | 3-0 | 2-0 | 3-1 | | 2-2 | 3-0 |
| Valladolid | 0-0 | 0-0 | 0-2 | 1-1 | 2-1 | 3-1 | 2-1 | 3-1 | 1-0 | 2-1 | 1-3 | 0-0 | 3-0 | 2-3 | 1-2 | 2-0 | | 1-1 |
| Zaragoza | 1-0 | 2-3 | 0-1 | 1-2 | 2-0 | 2-1 | 1-1 | 2-3 | 1-6 | 3-1 | 0-0 | 0-1 | 2-0 | 2-0 | 0-0 | 1-1 | 1-1 | |
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