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

Cambridge United announced they would have friendlies against Cardiff City,[2] Newmarket Town,[2] Brentford XI,[3] Queens Park Rangers,[2] AFC Sudbury[2] and Northampton Town[2] as part of their pre-season preparations.

Source: [citation needed] The U's fixtures were revealed on 24 June 2021.

[10][11] The U's were drawn into Southern Group H alongside Oxford United, Stevenage and Tottenham Hotspur U21s.

[12] In the knock-out stages, Cambridge were drawn at home to Portsmouth[13] and away to Rotherham United in the quarter-finals.