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

The team was led by 18th-year head coach Joye Lee-McNelis, and played their home games at the Reed Green Coliseum in Hattiesburg, Mississippi as a member of Conference USA (C-USA).

[1] On March 31, 2022, Southern Miss announced that this will be the last season for the team in the C-USA and will join the Sun Belt Conference on July 1, 2022.

[2] Source:[3]