The 2021–22 season was Exeter City's 120th year in their history, and their tenth and final consecutive season in League Two.

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

Source: [citation needed] The Grecians' fixtures were released on 24 June 2021.

[13] Exeter were drawn at home to Wycombe Wanderers in the first round.

[15][16] Exeter were drawn into Southern Group E alongside Bristol Rovers, Chelsea U21s and Cheltenham Town.