Since Round 15, 1906 Melbourne has suffered 26 losses by more than a hundred points, including the two largest defeats in VFL/AFL history.
| Margin | Opponent | Round | Venue | |
| 1 | 190 | Fitzroy | Round 17, 1979 | Waverley |
| 2 | 186 | Geelong | Round 19, 2011 | Kardinia Park |
| 3 | 148 | Essendon | Round 2, 2013 | MCG |
| 4 | 129 | North Melbourne | Round 10, 1981 | Waverley |
| 5 | 127 | North Melbourne | Round 14, 1990 | MCG |
| 5 | 127 | Geelong | Round 1, 1996 | MCG |
| 7 | 125 | Fitzroy | Round 16, 1919 | Brunswick Street |
| 8 | 124 | Sydney | Round 17, 1986 | SCG |
| 9 | 122 | Essendon | Round 15, 1986 | MCG |
| 9 | 122 | North Melbourne | Round 18, 2013 | Docklands |
| 11 | 120 | Footscray | Round 15, 1985 | Western Oval |
| 12 | 116 | Carlton | Round 10, 1986 | MCG |
| 12 | 116 | Sydney | Round 18, 1997 | MCG |
| 12 | 116 | Geelong | Round 19, 2008 | MCG |
| 15 | 115 | Hawthorn | Round 21, 1983 | Waverley |
| 16 | 113 | North Melbourne | Round 19, 1978 | Arden Street |
| 16 | 113 | North Melbourne | Round 17, 1996 | MCG |
| 18 | 111 | Geelong | Round 23, 2016 | Kardinia Park |
| 19 | 109 | Collingwood | Round 15, 1919 | Victoria Park |
| 20 | 108 | West Coast | Round 2, 2012 | Subiaco |
| 21 | 107 | Fitzroy | Round 15, 1906 | MCG |
| 21 | 107 | Footscray | Round 13, 1992 | Western Oval |
| 21 | 107 | Collingwood | Round 2, 1997 | MCG |
| 24 | 106 | West Coast | Round 6, 1996 | Princes Park |
| 25 | 105 | Hawthorn | Round 7, 2015 | MCG |
| 26 | 104 | Hawthorn | Round 1, 2008 | MCG |
| 27 | 101 | Sydney | Round 8, 2012 | SCG |
Opponent
5 - North Melbourne
4 - Geelong
3 - Fitzroy, Hawthorn, Sydney
2 - Collingwood, Essendon, Footscray, West Coast
1 - Carlton
Coaches
5 - John Northey
4 - Neale Balme
3 - Ron Barassi, Dean Bailey, Mark Neeld
2 - George Haines, Paul Roos
1 - Neil Craig, Denis Jones, Carl Ditterich, Greg Hutchison
Grounds
12 - MCG
3 - Waverley
2 - Kardinia Park, SCG, Western Oval
1 - Arden Street, Brunswick Street, Docklands, Princes Park, Subiaco, Victoria Park
Debuts in 100 point losses
| Player | Game | Margin | ||
| Charlie Taylor | Round 15, 1906 | 107 | ||
| Dave Elliman | Round 16, 1919 | 125 | ||
| Harry Selover | Round 16, 1919 | 125 | ||
| Frank Rugolo | Round 21, 1983 | 115 | ||
| Bret Hutchinson | Round 15, 1985 | 120 | ||
| Stephen Wearne | Round 13, 1992 | 107 | ||
| David Cockatoo-Collins | Round 1, 1996 | 127 | ||
| Donald Cockatoo-Collins | Round 1, 1996 | 127 | ||
| Cale Morton | Round 1, 2008 | 104 | ||
| Isaac Weetra | Round 1, 2008 | 104 | ||
| Dean Terlich | Round 2, 2013 | 148 | ||
Other top 50 losses
| Margin | Opponent | Round | Venue | |
| 28 | 98 | Carlton | Round 13, 2000 | MCG |
| 28 | 98 | Western Bulldogs | Round 20, 2015 | Docklands |
| 30 | 96 | Hawthorn | Grand Final 1988 | MCG |
| 31 | 95 | Geelong | Round 12, 1998 | MCG |
| 31 | 95 | Western Bulldogs | Round 2, 2008 | MCG |
| 31 | 95 | Collingwood | Round 10, 2013 | MCG |
| 34 | 94 | Collingwood | Round 2, 1996 | MCG |
| 34 | 94 | West Coast | Round 3, 2013 | MCG |
| 36 | 93 | West Coast | Round 2, 2014 | MCG |
| 36 | 93 | Richmond | Round 9, 1980 | MCG |
| 38 | 92 | Geelong | Round 3, 1982 | Kardinia Park |
| 38 | 92 | Fremantle | Round 14, 2024 | Traeger Park |
| 40 | 90 | Fremantle | Round 9, 2013 | Subiaco |
| 41 | 89 | Carlton | Round 5, 1919 | Princes Park |
| 41 | 89 | Carlton | Round 15, 1978 | Waverley |
| 41 | 89 | Port Adelaide | Round 17, 2007 | Football Park |
| 44 | 88 | Geelong | Round 16, 1981 | Geelong |
| 44 | 88 | St Kilda | Round 18, 2005 | MCG |
| 44 | 88 | Collingwood | Round 12, 2011 | MCG |
| 47 | 87 | Carlton | Round 17, 1905 | MCG |
| 47 | 87 | North Melbourne | Round 7, 1980 | Waverley |
| 49 | 86 | Fitzroy | Round 19, 1983 | Junction Oval |
| 49 | 86 | Carlton | Round 22, 1986 | Princes Park |
| 49 | 86 | St Kilda | Round 6, 1997 | Waverley |