Key: Win : Draw : Loss
| Date | Home | Away | Ref | ||
|---|---|---|---|---|---|
| 07/08/2010 | Southampton | 0 | 1 | Plymouth | J Moss |
| 21/08/2010 | Southampton | 1 | 1 | Leyton Orient | P Gibbs |
| 28/08/2010 | Bristol Rvs | 0 | 4 | Southampton | G Scott |
| 04/09/2010 | Southampton | 0 | 2 | Rochdale | A Woolmer |
| 11/09/2010 | Swindon | 1 | 0 | Southampton | A Penn |
| 15/09/2010 | Milton Keynes Dons | 2 | 0 | Southampton | F Graham |
| 18/09/2010 | Southampton | 0 | 0 | Colchester | G Horwood |
| 25/09/2010 | Sheffield Weds | 0 | 1 | Southampton | G Salisbury |
| 28/09/2010 | Yeovil | 1 | 1 | Southampton | S Hooper |
| 02/10/2010 | Southampton | 2 | 0 | Bournemouth | K Wright |
| 09/10/2010 | Southampton | 2 | 0 | Tranmere | G Ward |
| 16/10/2010 | Huddersfield | 2 | 0 | Southampton | C Webster |
| 23/10/2010 | Southampton | 2 | 1 | Oldham | A D'Urso |
| 30/10/2010 | Notts County | 1 | 3 | Southampton | J Waugh |
| 02/11/2010 | Southampton | 4 | 0 | Dag and Red | D McDermid |
| 13/11/2010 | Carlisle | 3 | 2 | Southampton | K Evans |
| 20/11/2010 | Southampton | 4 | 1 | Peterboro | C Sarginson |
| 23/11/2010 | Southampton | 0 | 0 | Brighton | I Williamson |
| 11/12/2010 | Southampton | 0 | 2 | Brentford | O Langford |
| 28/12/2010 | Southampton | 4 | 1 | Huddersfield | J Linnington |
| 01/01/2011 | Southampton | 4 | 0 | Exeter | D Phillips |
| 03/01/2011 | Dag and Red | 1 | 3 | Southampton | M Russell |
| 11/01/2011 | Oldham | 0 | 6 | Southampton | G Eltringham |
| 15/01/2011 | Southampton | 0 | 0 | Notts County | G Scott |
| 22/01/2011 | Tranmere | 2 | 0 | Southampton | D Webb |
| 01/02/2011 | Exeter | 1 | 2 | Southampton | D McDermid |
| 05/02/2011 | Peterboro | 4 | 4 | Southampton | E Ilderton |
| 12/02/2011 | Southampton | 1 | 0 | Carlisle | R Lewis |
| 22/02/2011 | Hartlepool | 0 | 0 | Southampton | S Mathieson |
| 26/02/2011 | Southampton | 4 | 1 | Swindon | S Rushton |
| 01/03/2011 | Walsall | 1 | 0 | Southampton | D Whitestone |
| 05/03/2011 | Colchester | 0 | 2 | Southampton | P Gibbs |
| 08/03/2011 | Southampton | 3 | 0 | Yeovil | K Hill |
| 12/03/2011 | Bournemouth | 1 | 3 | Southampton | A Marriner |
| 19/03/2011 | Southampton | 2 | 0 | Sheffield Weds | D Deadman |
| 22/03/2011 | Charlton | 1 | 1 | Southampton | A D'Urso |
| 02/04/2011 | Southampton | 3 | 2 | Milton Keynes Dons | M Russell |
| 05/04/2011 | Southampton | 2 | 0 | Charlton | A Bates |
| 09/04/2011 | Leyton Orient | 0 | 2 | Southampton | M Clattenburg |
| 12/04/2011 | Rochdale | 2 | 0 | Southampton | M Haywood |
| 16/04/2011 | Southampton | 1 | 0 | Bristol Rvs | D Whitestone |
| 23/04/2011 | Brighton | 1 | 2 | Southampton | S Mathieson |
| 25/04/2011 | Southampton | 2 | 0 | Hartlepool | S Hooper |
| 30/04/2011 | Brentford | 0 | 3 | Southampton | T Kettle |
| 02/05/2011 | Plymouth | 1 | 3 | Southampton | A Woolmer |
| 07/05/2011 | Southampton | 3 | 1 | Walsall | G Scott |