The 1980–81 FIBA European Cup Winners' Cup was the fifteenth edition of FIBA's 2nd-tier level European-wide professional club basketball competition, contested between national domestic cup champions, running from 7 October 1980, to 18 March 1981.

It was contested by 20 teams, two less than in the previous edition.

[1] Squibb Cantù defeated FC Barcelona, in the final held in Rome, winning the FIBA European Cup Winner's Cup for a (European record) fourth time.

*Union Récréation Alexandria withdrew before the second leg and Moderne received a forfeit (2-0).

March 18, Palaeur, Rome