During the 2021–22 season, Sheriff became the first Moldovan team to qualify for the group stages of the UEFA Champions League after a 3–0 aggregate win over Dinamo Zagreb. They were drawn into Group D to face Inter Milan, Real Madrid and Shakhtar Donetsk. On 15 September, Sheriff won their opening group game, 2–0 against Shakhtar Donetsk, before following it up with an upset 2–1 away victory over Real Madrid at the Santiago Bernabéu on 28 September 2021, with Sébastien Thill scoring the winning goal in the 89th minute.
