| 24 Aug 21 | r07        | LincolnLincoln | 3 - 2 | Man Utd U21Man Utd U21 |
| |
| 24 Aug 21 | r01        | ExeterExeter | 1 - 1 | Chelsea U21Chelsea U21 |
| 24 Aug 21 | r01        | ScunthorpeScunthorpe | 0 - 3 | Manchester City U21Manchester Ci |
| |
| 31 Aug 21 | r03        | AccringtonAccrington | 2 - 2 | BarrowBarrow |
| |
| 31 Aug 21 | r01        | CarlisleCarlisle | 3 - 3 | HartlepoolHartlepool |
| |
| 31 Aug 21 | r02        | Cambridge UnitedCambridge Uni | 4 - 1 | Oxford UtdOxford Utd |
| 31 Aug 21 | r02        | CharltonCharlton | 6 - 1 | CrawleyCrawley |
| 31 Aug 21 | r02        | Bristol RoversBristol Rover | 2 - 0 | CheltenhamCheltenham |
| 31 Aug 21 | r02        | Forest Green RoversForest Green | 1 - 1 | NorthamptonNorthampton |
| 31 Aug 21 | r02        | WycombeWycombe | 1 - 3 | Aston Villa U21Aston Villa U |
| 31 Aug 21 | r02        | Sheffield WedsSheffield Wed | 3 - 0 | Newcastle United U21Newcastle Uni |
| |
| 31 Aug 21 | r01        | BradfordBradford | 0 - 3 | LincolnLincoln |
| 31 Aug 21 | r01        | RochdaleRochdale | 4 - 0 | Liverpool U21Liverpool U21 |
| 31 Aug 21 | r01        | BoltonBolton | 3 - 2 | Port ValePort Vale |
| 31 Aug 21 | r01        | WiganWigan | 0 - 0 | Wolves U21Wolves U21 |
| 31 Aug 21 | r01        | ShrewsburyShrewsbury | 0 - 1 | CreweCrewe |
| 31 Aug 21 | r01        | OldhamOldham | 1 - 0 | Salford CitySalford City |
| |
| 31 Aug 21 | r02        | BurtonBurton | 1 - 2 | Milton Keynes DonsMilton Keynes |
| |
| 31 Aug 21 | r03        | NewportNewport | 2 - 0 | PlymouthPlymouth |
| |
| 31 Aug 21 | r02        | StevenageStevenage | 3 - 4 | Tottenham U21Tottenham U21 |
| 31 Aug 21 | r02        | Sutton UnitedSutton United | 3 - 0 | Crystal Palace U21Crystal Palac |
| |
| 31 Aug 21 | r03        | Harrogate Town FCHarrogate Tow | 3 - 1 | MansfieldMansfield |
| 31 Aug 21 | r03        | Fleetwood TownFleetwood Tow | 4 - 1 | Leicester U21Leicester U21 |
| |
| 07 Sep 21 | r02        | SwindonSwindon | 2 - 1 | Arsenal U21Arsenal U21 |
| |
| 07 Sep 21 | r03        | DoncasterDoncaster | 0 - 6 | RotherhamRotherham |
| 07 Sep 21 | r03        | ColchesterColchester | 0 - 1 | GillinghamGillingham |
| 07 Sep 21 | r03        | AFC WimbledonAFC Wimbledon | 5 - 3 | PortsmouthPortsmouth |
| |
| 14 Sep 21 | r04        | Leyton OrientLeyton Orient | 1 - 0 | Southampton U21Southampton U |
| |
| 14 Sep 21 | r03        | WalsallWalsall | 1 - 0 | Brighton U21Brighton U21 |
| 14 Sep 21 | r03        | TranmereTranmere | 4 - 1 | Leeds United U21Leeds United |
| 14 Sep 21 | r03        | MorecambeMorecambe | 0 - 1 | Everton U21Everton U21 |
| |
| 14 Sep 21 | r04        | IpswichIpswich | 1 - 2 | West Ham U21West Ham U21 |
| 21 Sep 21 | r04        | DoncasterDoncaster | 2 - 1 | Manchester City U21Manchester Ci |
| |
| 21 Sep 21 | r05        | BradfordBradford | 0 - 3 | Man Utd U21Man Utd U21 |
| |
| 21 Sep 21 | r04        | Cambridge UnitedCambridge Uni | 1 - 0 | Tottenham U21Tottenham U21 |
| 28 Sep 21 | r04        | OldhamOldham | 2 - 3 | Leeds United U21Leeds United |
| 28 Sep 21 | r04        | CarlisleCarlisle | 2 - 0 | Everton U21Everton U21 |
| 28 Sep 21 | r04        | ColchesterColchester | 1 - 0 | West Ham U21West Ham U21 |
| |
| 05 Oct 21 | r05        | LincolnLincoln | 1 - 2 | SunderlandSunderland |
| |
| 05 Oct 21 | r06        | AccringtonAccrington | 5 - 0 | Leicester U21Leicester U21 |
| |
| 05 Oct 21 | r04        | CreweCrewe | 2 - 0 | WiganWigan |
| 05 Oct 21 | r04        | Port ValePort Vale | 1 - 0 | RochdaleRochdale |
| |
| 05 Oct 21 | r05        | CheltenhamCheltenham | 2 - 2 | ExeterExeter |
| |
| 05 Oct 21 | r06        | CharltonCharlton | 4 - 1 | Southampton U21Southampton U |
| 05 Oct 21 | r06        | CrawleyCrawley | 0 - 4 | Leyton OrientLeyton Orient |
| 05 Oct 21 | r06        | NorthamptonNorthampton | 1 - 1 | WalsallWalsall |
| 05 Oct 21 | r06        | BurtonBurton | 2 - 4 | Aston Villa U21Aston Villa U |
| |
| 05 Oct 21 | r05        | Milton Keynes DonsMilton Keynes | 2 - 1 | WycombeWycombe |
| 05 Oct 21 | r05        | RotherhamRotherham | 4 - 1 | ScunthorpeScunthorpe |
| 05 Oct 21 | r05        | BoltonBolton | 4 - 1 | Liverpool U21Liverpool U21 |
| 05 Oct 21 | r05        | ShrewsburyShrewsbury | 3 - 1 | Wolves U21Wolves U21 |
| 05 Oct 21 | r05        | Salford CitySalford City | 0 - 2 | TranmereTranmere |
| 05 Oct 21 | r05        | HartlepoolHartlepool | 2 - 2 | MorecambeMorecambe |
| 05 Oct 21 | r05        | GillinghamGillingham | 0 - 2 | IpswichIpswich |
| |
| 05 Oct 21 | r06        | MansfieldMansfield | 1 - 2 | Sheffield WedsSheffield Wed |
| |
| 05 Oct 21 | r07        | Oxford UtdOxford Utd | 1 - 2 | StevenageStevenage |
| |
| 05 Oct 21 | r06        | Harrogate Town FCHarrogate Tow | 2 - 0 | Newcastle United U21Newcastle Uni |
| 05 Oct 21 | r06        | BarrowBarrow | 1 - 3 | Fleetwood TownFleetwood Tow |
| |
| 12 Oct 21 | r07        | Forest Green RoversForest Green | 2 - 2 | Brighton U21Brighton U21 |
| |
| 12 Oct 21 | r04        | Forest Green RoversForest Green | 2 - 2 | Brighton U21Brighton U21 |
| |
| 12 Oct 21 | r06        | NewportNewport | 3 - 4 | Arsenal U21Arsenal U21 |
| 12 Oct 21 | r06        | PlymouthPlymouth | 1 - 3 | SwindonSwindon |
| |
| 12 Oct 21 | r07        | PortsmouthPortsmouth | 0 - 2 | Sutton UnitedSutton United |
| |
| 13 Oct 21 | r00        | SunderlandSunderland | 2 - 1 | Man Utd U21Man Utd U21 |
| |
| 13 Oct 21 | r01        | SunderlandSunderland | 2 - 1 | Man Utd U21Man Utd U21 |
| |
| 13 Oct 21 | r07        | Bristol RoversBristol Rover | 1 - 2 | Chelsea U21Chelsea U21 |
| 26 Oct 21 | r07        | GillinghamGillingham | 0 - 2 | West Ham U21West Ham U21 |
| 26 Oct 21 | r07        | RotherhamRotherham | 5 - 0 | Manchester City U21Manchester Ci |
| |
| 26 Oct 21 | r08        | CheltenhamCheltenham | 0 - 0 | Chelsea U21Chelsea U21 |
| |
| 26 Oct 21 | r09        | Milton Keynes DonsMilton Keynes | 2 - 4 | Aston Villa U21Aston Villa U |
| |
| 26 Oct 21 | r07        | AFC WimbledonAFC Wimbledon | 0 - 2 | Crystal Palace U21Crystal Palac |
| 26 Oct 21 | r07        | Oxford UtdOxford Utd | 3 - 2 | Tottenham U21Tottenham U21 |
| 02 Nov 21 | r07        | Salford CitySalford City | 5 - 3 | Leeds United U21Leeds United |
| 02 Nov 21 | r07        | NorthamptonNorthampton | 1 - 2 | Brighton U21Brighton U21 |
| |
| 02 Nov 21 | r08        | RochdaleRochdale | 0 - 3 | BoltonBolton |
| 02 Nov 21 | r08        | HartlepoolHartlepool | 1 - 0 | Everton U21Everton U21 |
| |
| 02 Nov 21 | r10        | PlymouthPlymouth | 1 - 1 | Arsenal U21Arsenal U21 |
| |
| 09 Nov 21 | r08        | CreweCrewe | 3 - 0 | Wolves U21Wolves U21 |
| |
| 09 Nov 21 | r09        | StevenageStevenage | 1 - 0 | Cambridge UnitedCambridge Uni |
| 09 Nov 21 | r09        | Leyton OrientLeyton Orient | 1 - 0 | CharltonCharlton |
| 09 Nov 21 | r09        | CrawleyCrawley | 0 - 4 | Southampton U21Southampton U |
| 09 Nov 21 | r09        | SwindonSwindon | 1 - 0 | NewportNewport |
| 09 Nov 21 | r09        | WycombeWycombe | 0 - 5 | BurtonBurton |
| 09 Nov 21 | r09        | Sheffield WedsSheffield Wed | 4 - 0 | Harrogate Town FCHarrogate Tow |
| |
| 09 Nov 21 | r08        | SunderlandSunderland | 1 - 1 | BradfordBradford |
| 09 Nov 21 | r08        | ScunthorpeScunthorpe | 2 - 3 | DoncasterDoncaster |
| 09 Nov 21 | r08        | Port ValePort Vale | 5 - 0 | Liverpool U21Liverpool U21 |
| 09 Nov 21 | r08        | TranmereTranmere | 3 - 2 | OldhamOldham |
| 09 Nov 21 | r08        | MorecambeMorecambe | 0 - 2 | CarlisleCarlisle |
| |
| 09 Nov 21 | r09        | BarrowBarrow | 1 - 0 | Leicester U21Leicester U21 |
| |
| 09 Nov 21 | r10        | Sutton UnitedSutton United | 1 - 0 | AFC WimbledonAFC Wimbledon |
| 09 Nov 21 | r10        | IpswichIpswich | 0 - 0 | ColchesterColchester |
| 09 Nov 21 | r10        | MansfieldMansfield | 6 - 3 | Newcastle United U21Newcastle Uni |
| 09 Nov 21 | r10        | Fleetwood TownFleetwood Tow | 1 - 4 | AccringtonAccrington |
| 09 Nov 21 | r10        | PortsmouthPortsmouth | 3 - 0 | Crystal Palace U21Crystal Palac |
| |
| 10 Nov 21 | r09        | ExeterExeter | 5 - 3 | Bristol RoversBristol Rover |
| 10 Nov 21 | r09        | WalsallWalsall | 0 - 2 | Forest Green RoversForest Green |
| |
| 10 Nov 21 | r08        | WiganWigan | 2 - 0 | ShrewsburyShrewsbury |
| |
| 30 Nov 21 | r00        | BoltonBolton | 1 - 0 | Fleetwood TownFleetwood Tow |
| 30 Nov 21 | r00        | CarlisleCarlisle | 1 - 1 | LincolnLincoln |