The 2021–22 Wyoming Cowgirls basketball team represents the University of Wyoming in the 2021–22 college basketball season. The Cowgirls are led by head coach Gerald Mattinson, in his third season. The Cowgirls play their home games at the Arena-Auditorium and are members of the Mountain West Conference. The Cowgirls finished tied for 3rd in the Mountain West Conference, but exited the Mountain West Conference Women's Basketball tournament in the quarterfinal round, losing to Colorado State 51-38 due to an embarrassing 4th quarter performance.