The club takes its current name from its main sponsor, Sheriff, a company which operates nearly all forms of profitable private industries in Transnistria.

In the final at the Republican Stadium, Sheriff scored an injury-time equaliser before winning the match against Constructorul Chișinău 2–1 after extra time.

[5] Sheriff's first National Division title came in the 2000–01 season, which also included their second Moldovan Cup triumph as they beat Nistru Otaci on penalties after a goalless match.

Sheriff won each Moldovan Super Cup from 2004 to 2010, but did not have to play a match on four occasions due to winning it on default through a double.

In 2017, they qualified to the group stage for the fourth time, after beating favourites Legia Warsaw on away goals in the play-off round.

In the next round, Sheriff defeated Slavia Prague 1–1 on aggregate, progressing via the away goal rule due to Nadson's 94th-minute strike in the second leg.

[10] Dropping to the 2010–11 UEFA Europa League after their play-off defeat to Basel,[11] Sheriff was drawn into Group E alongside Dynamo Kyiv, AZ and BATE Borisov.

In the 2017–18 UEFA Europa League, Sheriff played in a group with Lokomotiv Moscow, Copenhagen, Fastav Zlín, in which they finished third once more.

In the 2021–22 UEFA Champions League, Sheriff became the first Moldovan team to qualify for the group stages of the competition after a 3–0 aggregate win over Dinamo Zagreb.

The departure of important players such as Cristiano da Silva Leite, Frank Castañeda, Danilo Arboleda, Dimitris Kolovos and Fernando Peixoto Costanza caused serious problems in the squad.

Sheriff replaced all the departures with new players like Regi Lushkja, Gaby Kiki, Renan Guedes and Patrick Kpozo.

Since the deadline for registration in the Europa League was February 2, coach Yuriy Vernydub was obliged to include players who had not played much in the starting line-up, such as Stjepan Radeljić, Stefanos Evangelou and Charles Petro.

They won 2–0 in the initial home leg – with the goal scorers being Sébastien Thill and Adama Traoré in a game where Sheriff put in a solid performance despite having a vastly different squad to the one that stunned Real Madrid.

[17] In June 2022, UEFA ordered that no European games would be permitted to be played in Transnistria, as a direct consequence of the 2022 Russian invasion of Ukraine.