The 2021–22 Southern Miss Lady Eagles basketball team represents the University of Southern Mississippi during the 2021–22 NCAA Division I women's basketball season. The team is led by eighteenth-year head coach Joye Lee-McNelis, and plays their home games at the Reed Green Coliseum in Hattiesburg, Mississippi as a member of Conference USA. On October 28, 2021, Southern Miss announced that this will be the last season for the team in the C-USA and become the Sun Belt Conference on July 1, 2022.