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

Notes: Carlisle United confirmed they would play friendly matches against Penrith,[6] Workington,[6] Hebburn Town,[6] Chorley,[6] Kendal Town,[6] Blackpool,[7] Everton U23s,[8] Lancaster City[6] and FC Halifax Town[8] as part of their pre-season preparations.

Source: [citation needed] Carlisle's fixtures were confirmed on 24 June 2021.

[14][15] The Cumbrians were drawn into Northern Group A alongside Everton U21s, Hartlepool United and Morecambe.

[15] In the knock-out stages, Carlisle were drawn away to Tranmere Rovers or Harrogate Town in the third round.