| First round |
| Walkover | 5th Kirkcudbrightshire Rifle Volunteers | | | | Cree Rovers | Scratched |
| 18 September 1880 | 17th Renfrew Rifle Volunteers | 6 | - | 1 | Wellington Park | |
| 18 September 1880 | Abercorn | 7 | - | 1 | Barrhead | |
| 18 September 1880 | Airdrie | 3 | - | 0 | Bellshill | |
| Walkover | Airdriehill | | | | Airdrie Bluebell | Scratched |
| 18 September 1880 | Alexandra Athletic | 4 | - | 1 | Kelvinbank | |
| Walkover | Arbroath | | | | Vale of Teith | Scratched |
| 4 September 1880 | Arthurlie | 2 | - | 0 | Johnstone | |
| 11 September 1880 | Athole | 1 | - | 1 | Whitefield | |
| 18 September 1880 | Auchinleck Boswell | 1 | - | 7 | Cumnock | |
| 11 September 1880 | Ayr | 2 | - | 0 | Catrine | |
| 11 September 1880 | Beith | 4 | - | 1 | Irvine | |
| 18 September 1880 | Caledonian | 1 | - | 2 | Clyde | |
| Walkover | Cambuslang | | | | Upper Clydesdale | Scratched |
| 18 September 1880 | Campsie Central | 2 | - | 0 | Bridge of Allan | |
| 18 September 1880 | Cartside | 6 | - | 2 | Kennishead | |
| Walkover | Cartvale | | | | Levern | Scratched |
| Walkover | City | | | | 19th Lanark Rifle Volunteers | Scratched |
| 4 September 1880 | Clarkston | 1 | - | 0 | Plains Bluebell | |
| 18 September 1880 | Coupar Angus | 4 | - | 1 | Strathmore | |
| 4 September 1880 | Cowlairs | 4 | - | 3 | Petershill | |
| 11 September 1880 | Dumbarton | 7 | - | 0 | Helensburgh Victoria | |
| 18 September 1880 | Dunfermline | 5 | - | 3 | Hanover | |
| Walkover | Dunkeld | | | | St Clement's | Scratched |
| 11 September 1880 | Excelsior | 3 | - | 0 | Drumpelier | |
| Walkover | Falkirk | | | | Campsie Athletic | Scratched |
| Walkover | Hamilton Academical | | | | Stonelaw | Scratched |
| Walkover | Harmonic | | | | Ailsa | Scratched |
| 11 September 1880 | Heart of Midlothian | 3 | - | 1 | Brunswick | |
| Walkover | Hurlford | | | | Ayr Thistle | Scratched |
| 11 September 1880 | Jamestown | 6 | - | 0 | Alcutha | |
| 18 September 1890 | Jordanhill | 1 | - | 0 | Windsor | |
| 18 September 1880 | Kilbirnie | 3 | - | 0 | Lanemark | |
| Walkover | Kilmarnock | | | | Stewarton Cunninghame | Scratched |
| Walkover | Kilmarnock Athletic | | | | Girvan | Scratched |
| 11 September 1880 | Kilmarnock Portland | 8 | - | 0 | Coylton Coila | |
| 18 September 1880 | King's Park | 1 | - | 0 | Strathblane | |
| 11 September 1880 | Lennox | 1 | - | 2 | Helensburgh | Match declared void |
| Walkover | Mauchline | | | | Dean | Scratched |
| 30 September 1880 | Maybole | 3 | - | 1 | Rankinston Volunteers | |
| 4 September 1880 | Milton of Campsie | 2 | - | 1 | Grasshoppers | |
| 18 September 1880 | Morton | 3 | - | 2 | Glenkilloch | |
| Walkover | Netherlee | | | | Oakfield | Scratched |
| 11 September 1880 | Northern | 3 | - | 1 | 3rd Lanark Rifle Volunteers | |
| 11 September 1880 | Oxford | 6 | - | 0 | Maxwell | |
| 18 September 1880 | Pilgrims | 4 | - | 2 | Lancefield | |
| Walkover | Partick Thistle | | | | Dennistoun | Scratched |
| 4 September 1880 | Pollok | 5 | - | 0 | Johnstone Rovers | |
| 11 September 1880 | Pollokshields Athletic | 0 | - | 4 | Partick | |
| Walkover | Possilpark | | | | High School | Scratched |
| 11 September 1880 | Queen's Park | 7 | - | 0 | John Elder | |
| 11 September 1880 | Rangers | 4 | - | 1 | Govan | |
| Walkover | Renton | | | | Kilmarnock Thistle | Scratched |
| 11 September 1880 | Rob Roy | 2 | - | 1 | Dundee Our Boys | |
| Walkover | Shawlands Athletic | | | | Clydesdale | Scratched |
| 11 September 1880 | Shotts | 4 | - | 0 | Lanark | |
| 11 September 1880 | South Western | 7 | - | 0 | Ingram | |
| 4 September 1880 | St Mirren | 3 | - | 0 | Johnstone Athletic | |
| 18 September 1880 | Star of Leven | 3 | - | 2 | Kirkintilloch Athletic | |
| 11 September 1880 | Stranraer | 3 | - | 0 | Queen of the South Wanderers | |
| 11 September 1880 | Thistle | 5 | - | 0 | Tolcross Athletic | |
| 18 September 1880 | Thornliebank | 3 | - | 0 | Renfrew | |
| 11 September 1880 | Uddingston | 2 | - | 2 | Royal Albert | |
| Walkover | Yoker | | | | Renfrew Ramblers | Scratched |
| Bye | Edinburgh University | | | | | |
| Bye | Glasgow University | | | | | |
| Bye | Glengowan | | | | | |
| Bye | Hibernian | | | | | |
| Bye | Lenzie | | | | | |
| Bye | Possil Bluebell | | | | | |
| Bye | Vale of Leven | | | | | |
| Replays |
| 25 September 1880 | Helensburgh | 8 | - | 1 | Lennox | |
| 18 September 1880 | Royal Albert | 5 | - | 0 | Uddingston | |
| 25 September 1880 | Whitefield | 1 | - | 2 | Athole | |
| Second round |
| 9 October 1880 | 5th Kirkcudbrightshire Rifle Volunteers | 4 | - | 3 | Stranraer | |
| 2 October 1880 | Abercorn | 4 | - | 2 | Morton | |
| 2 October 1880 | Airdrie | 3 | - | 2 | Excelsior | |
| 2 October 1880 | Alexandra Athletic | 1 | - | 0 | Athole | |
| 2 October 1880 | Arthurlie | 1 | - | 1 | Cartvale | |
| 9 October 1880 | Cambuslang | 3 | - | 1 | Hamilton Academical | |
| 2 October 1880 | Campsie Central | 5 | - | 5 | Milton of Campsie | |
| 2 October 1880 | Clarkston | 2 | - | 1 | Airdriehill | |
| 2 October 1880 | Coupar Angus | 1 | - | 2 | Arbroath | |
| 9 October 1880 | Cowlairs | 4 | - | 3 | Oxford | |
| 2 October 1880 | Dumbarton | 2 | - | 1 | Jamestown | |
| 2 October 1880 | Falkirk | 2 | - | 1 | King's Park | |
| 2 October 1880 | Glengowan | 1 | - | 1 | Thistle | |
| 2 October 1880 | Harmonic | 1 | - | 1 | Clyde | |
| 2 October 1880 | Helensburgh | 5 | - | 1 | Star of Leven | |
| 9 October 1880 | Hibernian | 3 | - | 1 | Dunfermline | |
| 2 October 1880 | Hurlford | 2 | - | 1 | Cumnock | |
| 2 October 1880 | Kilbirnie | 3 | - | 0 | Kilmarnock Thistle | Match declared void |
| 9 October 1880 | Kilmarnock | 6 | - | 3 | Ayr | |
| 2 October 1880 | Kilmarnock Portland | 0 | - | 1 | Beith | |
| 9 October 1880 | Mauchline | 6 | - | 1 | Maybole | |
| 2 October 1880 | Netherlee | 0 | - | 2 | Yoker | |
| 9 October 1880 | Partick Thistle | 1 | - | 0 | Jordanhill | |
| 9 October 1880 | Pilgrims | 7 | - | 0 | City | |
| 2 October 1880 | Queen's Park | 5 | - | 0 | Possilpark | |
| 2 October 1880 | Rangers | 1 | - | 0 | Northern | |
| 9 October 1880 | Renton | 0 | - | 1 | Vale of Leven | |
| 2 October 1880 | Rob Roy | 4 | - | 0 | Dunkeld | |
| 2 October 1880 | Royal Albert | 1 | - | 0 | Shotts | |
| Walkover | Shawlands Athletic | | | | Possil Bluebell | Scratched |
| 9 October 1880 | South Western | 2 | - | 0 | Partick | |
| 2 October 1880 | St Mirren | 3 | - | 2 | 17th Renfrew Rifle Volunteers | |
| 2 October 1880 | Thornliebank | 0 | - | 3 | Pollok | |
| Bye | Cartside | | | | | |
| Bye | Edinburgh University | | | | | |
| Bye | Glasgow University | | | | | |
| Bye | Heart of Midlothian | | | | | |
| Bye | Lenzie | | | | | |
| Replays |
| 9 October 1880 | Cartvale | 1 | - | 2 | Arthurlie | |
| 9 October 1880 | Clyde | 1 | - | 0 | Harmonic | |
| 16 October 1880 | Kilbirnie | 2 | - | 1 | Kilmarnock Thistle | |
| 9 October 1880 | Milton of Campsie | 1 | - | 3 | Campsie Central | |
| 9 October 1880 | Thistle | 6 | - | 1 | Glengowan | |
| Third round |
| 23 October 1880 | Abercorn | 1 | - | 4 | St Mirren | |
| 6 November 1880 | Alexandra Athletic | 1 | - | 2 | Cowlairs | |
| 6 November 1880 | Arbroath | 2 | - | 1 | Rob Roy | |
| 23 October 1880 | Arthurlie | 2 | - | 0 | Pollok | |
| 23 October 1880 | Beith | 17 | - | 2 | 5th Kirkcudbrightshire Rifle Volunteers | |
| 30 October 1880 | Campsie Central | 6 | - | 1 | Lenzie | |
| 30 October 1880 | Cartside | 4 | - | 3 | Yoker | |
| 23 October 1880 | Clyde | 3 | - | 0 | Shawlands Athletic | |
| 23 October 1880 | Dumbarton | 7 | - | 1 | Falkirk | |
| 23 October 1880 | Heart of Midlothian | 5 | - | 3 | Hibernian | |
| 23 October 1880 | Helensburgh | 1 | - | 4 | Vale of Leven | |
| 23 October 1880 | Kilbirnie | 0 | - | 2 | Hurlford | |
| 6 November 1880 | Mauchline | 3 | - | 3 | Kilmarnock | |
| 23 October 1880 | Queen's Park | 8 | - | 1 | Pilgrims | |
| 23 October 1880 | Rangers | 3 | - | 0 | Partick Thistle | |
| 23 October 1880 | Royal Albert | 0 | - | 5 | Cambuslang | |
| Walkover | Thistle | | | | Airdrie | Scratched |
| Bye | Clarkston | | | | | |
| Bye | Edinburgh University | | | | | |
| Bye | Glasgow University | | | | | |
| Bye | South Western | | | | | |
| Replays |
| 13 November 1880 | Kilmarnock | 0 | - | 3 | Mauchline | |
| Fourth round |
| 13 November 1880 | Arthurlie | 4 | - | 3 | South Western | Match declared void |
| 20 November 1880 | Cartside | 1 | - | 3 | Hurlford | |
| 13 November 1880 | Dumbarton | 9 | - | 0 | Glasgow University | |
| 13 November 1880 | Edinburgh University | 0 | - | 1 | Campsie Central | |
| 13 November 1880 | Heart of Midlothian | 3 | - | 0 | Cambuslang | |
| Walkover | Mauchline | | | | Clarkston | Scratched |
| 13 November 1880 | Queen's Park | 11 | - | 2 | Beith | |
| 13 November 1880 | Rangers | 11 | - | 0 | Clyde | |
| 13 November 1880 | St Mirren | 1 | - | 0 | Cowlairs | |
| Walkover | Vale of Leven | | | | Arbroath | Scratched |
| Bye | Thistle | | | | | |
| Replay |
| 27 November 1880 | Arthurlie | 1 | - | 1 | South Western | South Western disqualified |
| Fifth round |
| 11 December 1880 | Arthurlie | 4 | - | 0 | Heart of Midlothian | |
| 18 December 1880 | Hurlford | 0 | - | 3 | Rangers | |
| 11 December 1880 | Mauchline | 0 | - | 2 | Queen's Park | |
| 4 December 1880 | St Mirren | 1 | - | 5 | Dumbarton | |
| 4 December 1880 | Vale of Leven | 7 | - | 1 | Thistle | |
| Bye | Campsie Central | | | | | |
| Quarter-final |
| 25 December 1880 | Arthurlie | 0 | - | 2 | Vale of Leven | |
| 25 December 1880 | Campsie Central | 1 | - | 10 | Queen's Park | |
| 25 December 1880 | Rangers | 1 | - | 3 | Dumbarton | |
| Semi-final |
| 5 February 1881 | Vale of Leven | 0 | - | 2 | Dumbarton | |
| Bye | Queen's Park | | | | | |
| Final |
| 26 March 1881 | Queen's Park | 2 | - | 1 | Dumbarton | Played at Kinning Park, Glasgow |
| 15,000 | Match declared void after Dumbarton protested about spectators encroching on the pitch and a replay was ordered. Queen's Park also threatened to withdraw from the Scottish Football Association. The gates had to be closed during the replay. |
| Replay |
| 9 April 1881 | Queen's Park | 3 | - | 1 | Dumbarton | Played at Kinning Park, Glasgow |
| 10,000 | Smith (3) | | | | Meikleham | |
