They were led by 17th-year head coach Chris Mooney and played their home games at the Robins Center as members of the Atlantic 10 Conference.

6 seed, they defeated Rhode Island, VCU, Dayton, and Davidson to win the Atlantic 10 tournament.

On December 5, 2021, senior guard Jacob Gilyard set the new all-time NCAA Division I career steals record, securing his 386th steal to surpass Providence's John Linehan (385), whose record had stood since 2002.

[3] The Spiders received an at-large bid to the National Invitation Tournament, where they defeated Toledo in the first round[4] before losing to Mississippi State.

[5] With the NCAA granting student-athletes an extra year of eligibility due to impacts from the COVID-19 pandemic, three scholarship Spiders who would have otherwise exhausted their eligibility elected to return for the 2021–22 season: Jacob Gilyard, Nathan Cayo, and Grant Golden.