| Tuesday 26th August 1980 | |||
| 1st Leg | |||
| Birmingham City | 2-1 | Bristol City | |
| Bolton Wanderers | 0-3 | Crystal Palace | |
| Brighton and Hove A | 3-1 | Tranmere Rovers | |
| Burnley | 0-2 | West Ham United | |
| Cambridge United | 3-1 | Wolverhampton Wndrs | |
| Carlisle United | 1-2 | Charlton Athletic | |
| Chesterfield | 3-1 | Oxford United | |
| Everton | 3-0 | Blackpool | |
| Mansfield Town | 0-0 | Barnsley | |
| Middlesbrough | 3-1 | Ipswich Town | |
| Newport County | 1-1 | Notts County | |
| Oldham Athletic | 3-2 | Portsmouth | |
| Preston North End | 1-0 | Wigan Athletic | |
| Queens Park Rangers | 0-0 | Derby County | |
| Shrewsbury Town | 1-1 | Norwich City | |
| Southampton | 4-0 | Watford | |
| Swansea City | 1-1 | Arsenal | |
| West Bromwich Albion | 1-0 | Leicester City | |
| Wimbledon | 2-1 | Sheffield Wednesday | |
| Wednesday 27th August 1980 | |||
| 1st Leg | |||
| Aston Villa | 1-0 | Leeds United | |
| Blackburn Rovers | 0-0 | Gillingham | |
| Bradford City | 1-0 | Liverpool | |
| Cardiff City | 1-0 | Chelsea | |
| Leyton Orient | 0-1 | Tottenham Hotspur | |
| Lincoln City | 1-1 | Swindon Town | |
| Manchester United | 0-1 | Coventry City | |
| Newcastle United | 3-2 | Bury | |
| Nottingham Forest | 3-0 | Peterborough United | |
| Reading | 0-2 | Luton Town | |
| Stockport County | 1-1 | Sunderland | |
| Stoke City | 1-1 | Manchester City | |
| York City | 2-1 | Bristol Rovers | |
| Tuesday 2nd September 1980 | |||
| 2nd Leg | |||
| Arsenal | 3-1 | Swansea City | (4-2) |
| Barnsley | 4-2 | Mansfield Town | aet (4-2) |
| Bristol City | 0-0 | Birmingham City | (1-2) |
| Bury | 1-0 | Newcastle United | aet (3-3) |
| (Bury won on away goals) | |||
| Charlton Athletic | 2-1 | Carlisle United | (4-2) |
| Coventry City | 1-0 | Manchester United | (2-0) |
| Crystal Palace | 2-1 | Bolton Wanderers | (5-1) |
| Gillingham | 1-2 | Blackburn Rovers | aet (1-2) |
| Ipswich Town | 3-0 | Middlesbrough | (4-3) |
| Liverpool | 4-0 | Bradford City | (4-1) |
| Luton Town | 1-1 | Reading | (3-1) |
| Notts County | 2-0 | Newport County | (3-1) |
| Portsmouth | 1-0 | Oldham Athletic | aet (3-3) |
| (Portsmouth won on away goals) | |||
| Sheffield Wednesday | 3-1 | Wimbledon | (4-3) |
| Swindon Town | 2-0 | Lincoln City | (3-1) |
| Watford | 7-1 | Southampton | aet (7-5) |
| West Ham United | 4-0 | Burnley | (6-0) |
| Wolverhampton Wndrs | 0-1 | Cambridge United | (1-4) |
| Wednesday 3rd September 1980 | |||
| 2nd Leg | |||
| Blackpool | 2-2 | Everton | (2-5) |
| Bristol Rovers | 1-0 | York City | aet (2-2) |
| (Bristol Rovers won on away goals) | |||
| Chelsea | 1-1 | Cardiff City | (1-2) |
| Derby County | 0-0 | Queens Park Rangers | aet (0-0) |
| (Queens Park Rangers won on penalties) | |||
| Leeds United | 1-3 | Aston Villa | (1-4) |
| Leicester City | 0-1 | West Bromwich Albion | (0-2) |
| Manchester City | 3-0 | Stoke City | (4-1) |
| Norwich City | 2-0 | Shrewsbury Town | aet (3-1) |
| Oxford United | 3-0 | Chesterfield | (4-3) |
| Peterborough United | 1-1 | Nottingham Forest | (1-4) |
| Sunderland | 1-2 | Stockport County | (2-3) |
| Tottenham Hotspur | 3-1 | Leyton Orient | (4-1) |
| Tranmere Rovers | 2-4 | Brighton and Hove A | (3-7) |
| Wigan Athletic | 1-2 | Preston North End | (1-3) |
