Key: F - Friendlies; T - Tournament; L - League; CL - Champions League; CC - Carling Cup; FA - FA Cup
| Date | Opponents | Home/Away | Competition | Score | Position | Scorers |
|
15/07 |
Orlando Pirates | A | F | 4-0 | - | Solskjaer 2, Richardson, one own goal |
| 18/07 | Kaiser Chiefs | A | F | 1-0 | - | Dong Fangzhuo |
| 22/07 | Kaiser Chiefs | A | F | 0-0 | - | lost 4-3 on penalties |
| 26/07 | Celtic | A | F | 3-0 | - | Evans, Scholes 2 |
| 29/07 | Preston | A | F | 1-2 | - | Solskjaer |
| 31/07 | Macclesfield | A | F | 2-1 | - | Rooney, Campbell |
| 03/08 | Porto | A | F | 3-1 | - | Scholes, Rooney, Solskjaer, |
| 05/08 | Ajax | A | F | 1-0 | - | Giggs |
| 09/08 | Oxford United | A | F | 4-1 | - | Ronaldo 2; Solskjaer, Fletcher |
| 12/08 | Sevilla | H | F | 3-0 | - | Saha, Ronaldo, Jones |
| 20/08 | Fulham | H | L | 5-1 | 1 | Saha, Pearce (og); Rooney 2; Ronaldo |
| 23/08 | Charlton | A | L | 3-0 | 1 | Fletcher, Saha, Solskjaer |
| 26/08 | Watford | A | L | 2-1 | 1 | Silvestre, Giggs |
| 09/09 | Tottenham | H | L | 1-0 | 1 | Giggs |
| 13/09 | Celtic | H | CL | 3-2 | - | Saha 2, Solksjaer |
| 17/09 | Arsenal | H | L | 0-1 | 3 | - |
| 23/09 | Reading | A | L | 1-1 | 3 | Ronaldo |
| 26/09 | Benfica | A | CL | 1-0 | - | Saha |
| 01/10 | Newcastle | H | L | 2-0 | 2 | Solskjaer (2) |
| 14/10 | Wigan | A | L | 3-1 | 1 | Vidic, Saha, Solskjaer |
| 17/10 | FC Copenhagen | A | CL | 3-0 | - | Scholes, OShea, Richardson |
| 22/10 | Liverpool | H | L | 2-0 | 1 | Scholes, Ferdinand |
| 24/10 | Crewe | A | CC | 2-1 | - | Solskjaer, Lee (AET) |
| 28/10 | Bolton | A | L | 4-0 | 1 | Rooney 3; Ronaldo |
| 01/11 | FC Copenhagen | A | CL | 0-1 | - | - |
| 04/11 | Portsmouth | H | L | 3-0 | 1 | Saha, Ronaldo, Vidic |
| 07/11 | Southend | A | CC | 0-1 | - | - |
| 11/11 | Blackburn | A | L | 1-0 | 1 | Saha |
| 18/11 | Sheff United | A | L | 2-1 | 1 | Rooney 2 |
| 21/11 | Celtic | A | CL | 0-1 | - | - |
| 26/11 | Chelsea | H | L | 1-1 | 1 | Saha |
| 29/11 | Everton | H | L | 3-0 | 1 | Ronaldo, Evra, O'Shea |
| 02/12 | Middlesbrough | A | L | 2-1 | 1 | Saha, Fletcher |
| 06/12 | Benfica | H | CL | 3-1 | - | Vidic, Giggs, Saha |
| 09/12 | Man City | H | L | 3-1 | 1 | Rooney, Saha, Ronaldo |
| 17/12 | West Ham | A | L | 0-1 | 1 | - |
| 23/12 | Aston Villa | A | L | 3-0 | 1 | Ronaldo 2, Scholes |
| 26/12 | Wigan | H | L | 3-1 | 1 | Ronaldo 2, Solskjaer |
| 30/12 | Reading | H | L | 3-2 | 1 | Solskjaer, Ronaldo 2 |
| 01/07 | Newcastle | A | L | 2-2 | 1 | Scholes 2 |
| 07/07 | Aston Villa | H | FA3 | 2-1 | - | Larsson, Solskjaer |
| 13/07 | Aston Villa | H | L | 3-1 | 1 | Park, Carrick, Ronaldo |
| 21/01 | Arsenal | A | L | 1-2 | 1 | Rooney |
| 27/01 | Portsmouth | H | FA4 | 2-1 | - | Rooney 2 |
| 31/01 | Watford | H | L | 4-0 | 1 | Ronaldo, Doyley (og), Larsson, Rooney |
| 04/02 | Tottenham | A | L | 4-0 | 1 | Ronaldo, Vidic, Scholes, Giggs |
| 10/02 | Charlton | H | L | 2-0 | 1 | Park, Fletcher |
| 17/02 | Reading | H | FA5 | 1-1 | - | Carrick |
| 20/02 | Lille | A | CL | 1-0 | - | Giggs |
| 24/02 | Fulham | A | L | 2-1 | 1 | Giggs, Ronaldo |
| 27/02 | Reading | A | FA5 | 3-2 | - | Heinze, Saha, Solskjaer |
| 03/03 | Liverpool | A | L | 1-0 | 1 | O'Shea |
| 07/03 | Lille | H | CL | 1-0 | - | Larsson |
| 10/03 | Middlesbrough | A | FAQF | 2-2 | - | Rooney, Ronaldo |
| 13/03 | Europe XI | H | F | 4-3 | - | |
| 17/03 | Bolton | H | L | 4-1 | 1 | Park 2, Rooney 2 |
| 19/03 | Middlesbrough | H | FAQF | 1-0 | - | Ronaldo |
| 31/03 | Blackburn | H | L | 4-1 | 1 | Scholes, Carrick, Park, Solskjaer |
| 04/04 | Roma | A | CL | 1-2 | - | Rooney |
| 07/04 | Portsmouth | A | L | 1-2 | 1 | O'Shea |
| 10/04 | Roma | H | CL | 7-1 | - | Carrick 2, Ronaldo 2, Rooney, Smith, Evra |
| 14/04 | Watford | N | FASF | 4-1 | - | Rooney 2, Ronaldo, Richardson |
| 17/04 | Sheff United | H | L | 2-0 | 1 | Carrick, Rooney |
| 21/04 | Middlesbrough | H | L | 1-1 | 1 | Richardson |
| 24/04 | AC Milan | H | CLSF | 3-2 | - | Ronaldo, Rooney 2 |
| 28/04 | Everton | A | L | 4-2 | 1 | O'Shea, P.Neville (og), Rooney, Eagles |
| 02/05 | AC Milan | A | CLSF | 0-3 | - | - |
| 05/05 | Man City | A | L | 1-0 | 1 | Ronaldo CHAMPIONS!!! |
| 09/05 | Chelsea | A | L | 0-0 | 1 | - |
| 13/05 | West Ham | H | L | 0-1 | 1 | |
| 19/05 | Chelsea | Wembley | FA Cup Final | 0-1 | - |