The 1980–81 season of the European Cup Winners' Cup was won by Dinamo Tbilisi in the final against Carl Zeiss Jena. Dinamo Tbilisi's side defeated English Second Division side West Ham United away before beating Carl Zeiss Jena in a final watched by 4,750 people in Düsseldorf. This win was the high point of the Georgian side and is still the club's greatest achievement.
The competition included the Real Madrid reserve team, Castilla CF, who qualified as the runners-up of the 1979–80 Copa del Rey.
Celtic won 7–2 on aggregate.
Benfica won 4–0 on aggregate.
Hvidovre won 3–0 on aggregate.
2–2 on aggregate; Politehnica Timișoara won on away goals.
Carl Zeiss Jena won 4–3 on aggregate.
Dinamo Tbilisi won 2–0 on aggregate.
Waterschei Thor won 7–1 on aggregate.
Benfica won 2–0 on aggregate.
Newport County won 6–0 on aggregate.
West Ham United won 4–1 on aggregate.
Feyenoord won 3–1 on aggregate.
Carl Zeiss Jena won 3–2 on aggregate.
Benfica won 2–1 on aggregate.
Dinamo Tbilisi won 4–2 on aggregate.
Feyenoord won 6–3 on aggregate.
Carl Zeiss Jena won 3–2 on aggregate.
Benfica won 3–2 on aggregate.
Dinamo Tbilisi won 3–2 on aggregate.
Carl Zeiss Jena won 2–1 on aggregate.