The 1981 Copa Interamericana was the 8th edition of the Copa Interamericana. The match-up featured Mexican club UNAM, the winners of the 1980 CONCACAF Champions' Cup, and Uruguayan club Nacional, the winners of the 1980 Copa Libertadores. It was played staged over two legs. UNAM defeated Nacional 6–5 on aggregate following a play-off to win their first Copa Interamericana title.