The Huskies returned three seniors and sophomore consensus 2020–21 NCAA player of the year Paige Bueckers, while adding a 2nd ranked recruiting class.

Bueckers, the team's leading scorer, won several awards at the end of the season, including the Naismith College Player of the Year.

The Huskies lost guards Autumn Chassion and Anna Makurat after the end of the previous season but graduated no seniors.

Chassion, who had earned a place on the squad as a walk-on and played in eight games, chose to transfer to Louisiana State University at Eunice after the end of her freshman year.

[5][6][7] Makurat, who had played in 48 games in her two seasons, ended her time at UConn having averaged 6.5 points, 3.7 rebounds, and 3.0 assists per game[8] and after entering the NCAA transfer portal, chose instead to return to her native Poland and play professional basketball with AZS AJP Gorzów Wielkopolski of the Basket Liga Kobiet.

[9] After the Huskies' first game, freshman Saylor Poffenbarger chose to transfer[10] and then committed to play for Arkansas in late November.

[11] On December 13, sophomore forward Mir McLean announced she would be leaving the team at the end of the fall term and later transferred to Virginia.

[16] They again signed the top-ranked high school player in Azzi Fudd[16] and added rangy guard Caroline Ducharme[17] and 6-foot-5 forward Amari DeBerry.

[16] Saylor Poffenbarger started school during the 2021 spring semester and joined the team in January,[18] but she decided to transfer to Arkansas in November 2021.

[24] At the season's outset, the Huskies returned several starters: seniors Christyn Williams, Olivia Nelson-Ododa, and Evina Westbrook, plus accomplished sophomore Paige Bueckers.

[25][26] Two-time All-Big Ten forward Dorka Juhász, an Ohio State graduate transfer, was expected to add experience and depth in the post.

Highly touted freshman recruits Azzi Fudd, Amari DeBerry, Caroline Ducharme, and Saylor Poffenbarger were expected to compete for playing time.

[27][28] In the season's opening weeks, Griffin was affected by a back problem and missed the entire year due to injury.

Towards the end of the team's sixth game, Bueckers suffered a tibial plateau fracture[30] and after surgery was forced to sit out most of the regular season, only returning before the Big East Conference tournament, where she played limited minutes.

At the Bridgeport regional, the Huskies took a lead in the second quarter against 3rd seed Indiana and never looked back, advancing to a record 16th consecutive Elite Eight.

In the national championship game, South Carolina jumped out to an 18-point lead while dominating the boards and held off scoring runs to defeat UConn.