The 1980–81 Yugoslav First League season was the 35th season of the First Federal League (Serbo-Croatian: Prva savezna liga), the top level association football competition of SFR Yugoslavia, since its establishment in 1946.
A total of 18 teams competed in the league, with the previous season's champions Red Star successfully defending their title, finishing the season two points clear of runners-up Hajduk Split.
A total of eighteen teams contested the league, including sixteen sides from the 1979–80 season and two sides promoted from the 1979–80 Yugoslav Second League (YSL) as winners of the two second level divisions East and West.
The league was contested in a double round robin format, with each club playing every other club twice, for a total of 34 rounds.
The two clubs promoted were NK Zagreb and OFK Belgrade, returning to the top level after being relegated in the 1978–79 season.