They lost only twice, both of which came in consecutive matches in the UEFA Women's Champions League knockout stages, losing 0–2 against Wolfsburg in the second leg of the semi-finals, but winning 5–3 on aggregate and getting through to the final.

Last updated: 29 May 2022 Source: Competitions Barcelona opened the pre-season with a Joan Gamper Trophy victory against Italian champions Juventus.

They travelled to the United States for the 2021 Women's International Champions Cup to face French Division 1 Féminine Lyon and NWSL side Houston Dash at Providence Park in Portland.

Barcelona faced Real Madrid in the first semi-final, edging out a 1–0 win with a goal by Alexia in the dying minutes of the game.

The group stage draw was completed on 13 September 2021, and Barcelona started its title defense against English club Arsenal.

Barcelona held the quarter-final, 2nd leg, against Women's Clásico rival Real Madrid at Camp Nou, the home team's second competitive match at the stadium and the first in front of fans.