The 1980–81 NCAA Division I men's basketball season began on November 28, 1980, progressed through the regular season and conference tournaments, and concluded with the 1981 NCAA Men's Division I Basketball Tournament Championship Game on March 30, 1981, at The Spectrum in Philadelphia. The Indiana Hoosiers won their fourth NCAA national championship with a 63–50 victory over the North Carolina Tar Heels.

The top 20 from the AP and UPI polls during the pre-season.

Note: From 1975 to 1982, the Eastern College Athletic Conference (ECAC), a loosely organized sports federation of Northeastern colleges and universities, organized Division I ECAC regional tournaments for those of its members that were independents in basketball. Each 1981 tournament winner received an automatic bid to the 1981 NCAA Men's Division I Basketball Tournament in the same way that the tournament champions of conventional athletic conferences did. The ECAC North was a separate, conventional conference.

Indiana won its fourth NCAA title with a 63–50 win over North Carolina and coach Dean Smith. Precocious sophomore Isiah Thomas was named Final Four Most Outstanding Player in a title game delayed due to the shooting of President Ronald Reagan.