Madonna’s 40 Biggest Billboard Hits is based on actual performances on the weekly Billboard Hot 100 chart. Songs are ranked based on an inverse point system, with weeks at No. 1 earning the greatest value and weeks at No.100 earning the least.
| Rank | Title | Peak position | Year |
| 40 | Rain | 14 | 1993 |
| 39 | Oh Father | 20 | 1990 |
| 38 | Don’t Cry for Me Argentina | 8 | 1997 |
| 37 | Holiday | 16 | 1984 |
| 36 | Hanky Panky | 10 | 1990 |
| 35 | Erotica | 3 | 1992 |
| 34 | Don’t Tell Me | 4 | 2001 |
| 33 | Lucky Star | 4 | 1984 |
| 32 | Dress You Up | 5 | 1985 |
| 31 | Rescue Me | 9 | 1991 |
| 30 | Hung Up | 7 | 2005 |
| 29 | Die Another Die | 8 | 2002 |
| 28 | Ray of Light | 5 | 1998 |
| 27 | Deeper and Deeper | 7 | 1993 |
| 26 | Keep It Together | 8 | 1990 |
| 25 | 4 Minutes | 3 | 2008 |
| 24 | Secret | 3 | 1994 |
| 23 | La Isla Bonita | 4 | 1987 |
| 22 | You’ll See | 6 | 1995 |
| 21 | Borderline | 10 | 1984 |
| 20 | Frozen | 2 | 1998 |
| 19 | This Used to Be My Playground | 1 | 1992 |
| 18 | Angel | 5 | 1985 |
| 17 | Cherish | 2 | 1989 |
| 16 | Express Yourself | 2 | 1989 |
| 15 | Material Girl | 2 | 1985 |
| 14 | Who’s That Girl | 1 | 1987 |
| 13 | True Blue | 3 | 1986 |
| 12 | Causing a Commotion | 2 | 1987 |
| 11 | I’ll Remember | 2 | 1994 |
| 10 | Open Your Heart | 1 | 1987 |
| 9 | Music | 1 | 2000 |
| 8 | Live To Tell | 1 | 1986 |
| 7 | Papa Don’t Preach | 1 | 1986 |
| 6 | Justify My Love | 1 | 1991 |
| 5 | Vogue | 1 | 1990 |
| 4 | Like A Prayer | 1 | 1989 |
| 3 | Take A Bow | 1 | 1995 |
| 2 | Crazy For You | 1 | 1985 |
| 1 | Like A Virgin | 1 | 1984 |