The 2021–22 Southern Miss Golden Eagles basketball team represented the University of Southern Mississippi during the 2021–22 NCAA Division I men's basketball season.

The team was led by third-year head coach Jay Ladner, and played their home games at Reed Green Coliseum in Hattiesburg, Mississippi as members of Conference USA (C-USA).

On October 28, 2021, Southern Miss announced that this would be the last season for the team in the C-USA and they would become a member of the Sun Belt Conference on July 1, 2022.

In a season limited due to the ongoing COVID-19 pandemic, the Golden Eagles finished the 2020–21 season 8–17, 4–13 in C-USA play last place in West Division.

They lost in the first round of the C-USA tournament to Rice.