Key: F - Friendlies; T - Tournament; L - League; CL - Champions League; CC - Carling Cup; FA - FA Cup
| Date | Opponents | Home/Away | Competition | Score | Position | Scorers |
| 17/07 | Urawa Red Diamonds | A | F | 2-2 | - | Fletcher, Ronaldo |
| 20/07 | FC Seoul | A | F | 4-0 | - | Ronaldo, Eagles, Rooney, Evra |
| 23/07 | Shenzhen | A | F | 6-0 | - | Giggs, Rooney, Nani, O'Shea, Ronaldo, Eagles |
| 25/07 | Port Vale | A | F | 2-3 | - | Rossi, Campbell |
| 27/07 | Guangzhou | A | F | 3-0 | - | Rooney, Nani, Martin |
| 01/08 | Inter Milan | H | F | 2-3 | - | Rooney, Adriano (og) |
| 03/08 | Doncaster | A | F | 2-0 | - | Gibson, S Evans |
| 04/08 | Peterborough | A | F | 3-1 | - | Eckersley, R Jones, Dong |
| 05/08 | Chelsea | Wembley | C Shield | 1-1 | - | Giggs. Won 3-0 on penalties |
| 08/08 | Glentoran | A | F | 3-0 | - | Campbell, Evra, Nani |
| 08/08 | Dunfermline | A | F | 4-0 | - | Rooney 2, Eagles, Giggs |
| 12/08 | Reading | H | L | 0-0 | - | |
| 15/08 | Portsmouth | A | L | 1-1 | - | Scholes |
| 19/08 | Man City | A | L | 0-1 | 16 | - |
| 26/08 | Tottenham Hotspur | H | L | 1-0 | 10 | Nani |
| 01/09 | Sunderland | H | L | 1-0 | 8 | Saha |
| 15/09 | Everton | A | L | 1-0 | 2 | Vidic |
| 19/09 | Sporting Lisbon | A | L | 1-0 | - | Ronaldo |
| 26/09 | Coventry | H | CC | 0-2 | - | - |
| 29/09 | Birmingham | A | L | 1-0 | 2 | Ronaldo |
| 02/10 | Roma | H | CL | 1-0 | - | Rooney |
| 06/10 | Wigan | H | L | 4-0 | 2 | Tevez, Ronaldo 2, Rooney |
| 20/10 | Aston Villa | A | L | 4-1 | 2 | Rooney 2, Ferdinand, Giggs |
| 23/10 | Dynamo Kiev | A | CL | 4-2 | - | Ferdinand, Rooney, Ronaldo 2 |
| 27/10 | Middlesbrough | H | L | 4-1 | 2 | Nani, Rooney, Tevez 2 |
| 03/11 | Arsenal | A | L | 2-2 | 2 | Rooney, Ronaldo |
| 11/11 | Blackburn | H | L | 2-0 | 1 | Ronaldo 2 |
| 24/11 | Bolton | A | L | 0-1 | 2 | - |
| 27/11 | Sporting Lisbon | H | CL | 2-1 | - | Tevez, Ronaldo |
| 03/12 | Fulham | H | L | 2-0 | 2 | Ronaldo 2 |
| 08/12 | Derby Co | H | L | 4-1 | 2 | Giggs, Tevez 2, Ronaldo |
| 12/12 | Roma | A | CL | 1-1 | - | Pique |
| 16/12 | Liverpool | A | L | 1-0 | 2 | Tevez |
| 23/12 | Everton | H | L | 2-1 | 1 | Ronaldo 2 |
| 26/12 | Sunderland | A | L | 4-0 | 1 | Rooney, Saha 2, Ronaldo |
| 29/12 | West Ham | A | L | 1-2 | 2 | Ronaldo |
| 01/01 | Birmingham | H | L | 1-0 | 2 | Tevez |
| 05/01 | Aston Villa | A | FA3 | 2-0 | - | Ronaldo, Rooney |
| 12/01 | Newcastle | H | L | 6-0 | 1 | Ronaldo 3; Tevez 2, Ferdinand |
| 19/01 | Reading | A | L | 2-0 | 1 | Rooney, Ronaldo |
| 26/01 | Tottenham | H | FA4 | 3-1 | - | Ronaldo 2, Tevez |
| 30/01 | Portsmouth | H | L | 2-0 | 1 | Ronaldo 2 |
| 02/02 | Tottenham | A | L | 1-1 | 2 | Tevez |
| 10/02 | Man City | H | L | 1-2 | 2 | Carrick |
| 16/02 | Arsenal | H | FA5 | 4-0 | - | Fletcher 2, Rooney, Nani |
| 20/02 | Lyon | A | CL | 1-1 | - | Tevez |
| 23/02 | Newcastle | A | L | 5-1 | 2 | Rooney 2, Ronaldo 2, Saha |
| 01/03 | Fulham | A | L | 3-0 | 1 | Hargreaves, Park, Davis (og) |
| 04/03 | Lyon | H | CL | 1-0 | - | Ronaldo |
| 08/03 | Portsmouth | H | FAQF | 0-1 | - | - |
| 15/03 | Derby Co | A | L | 1-0 | 1 | Ronaldo |
| 19/03 | Bolton | H | L | 2-0 | 1 | Ronaldo 2 |
| 23/03 | Liverpool | H | L | 3-0 | 1 | Brown, Ronaldo, Nani |
| 29/03 | Aston Villa | H | L | 4-0 | 1 | Ronaldo, Tevez, Rooney 2 |
| 01/04 | Roma | A | CLQF | 2-0 | - | Ronaldo, Rooney |
| 06/04 | Middlesbrough | A | L | 2-2 | 1 | Ronaldo, Rooney |
| 09/04 | Roma | H | CLQF | 1-0 | - | Tevez |
| 13/04 | Arsenal | H | L | 2-1 | 1 | Ronaldo, Hargreaves |
| 19/04 | Blackburn | A | L | 1-1 | 1 | Tevez |
| 23/04 | Barcelona | A | CLSF | 0-0 | - | |
| 26/04 | Chelsea | A | L | 1-2 | 1 | Rooney |
| 29/06 | Barcelona | H | CLSF | 1-0 | Scholes | |
| 03/05 | West Ham | H | L | 4-1 | 1 | Ronaldo 2, Tevez, Carrick |
| 11/05 | Wigan | A | L | 2-0 | 1 | Ronaldo, Giggs |
| 23/05 | Chelsea | Moscow | CL Final | 1-1 | - | United won 6-5 on penalties AET |