The season covers the period from 1 July 2021 to 30 June 2022.

During pre-season, Micky Mellon returned to the club as he was announced as the new manager.

[1] Tranmere Rovers announced they would have a friendly against Rangers,[2] Stalybridge Celtic,[3] Warrington Town[3] and Sunderland[4] as part of their pre-season preparations.

Source: [citation needed] Tranmere Rovers' league fixtures were revealed on 24 June 2021.

[9] Rovers were drawn away to Oldham Athletic in the first round.