| Rank | Location | Death Toll | Event | Year | |
|---|
| 1 | Worldwide | 500,000,000 | Smallpox | 1950 | |
| 2 | Asia, Europe, Africa | 100,000,000 | Bubonic Plague: Black Death | 1300 | |
| 3 | Worldwide | 200,000,000 | Measles | 1850 | |
| 4 | Worldwide | 80,000,000 | Malaria | 1900 | |
| 5 | Worldwide | 50,000,000 | Spanish Flu | 1918 | |
| 6 | Worldwide | 40,000,000 | Tuberculosis | 1900 | |
| 7 | Asia, Europe, Africa | 40,000,000 | Bubonic Plague: Plague of Justinian | 540 | |
| 8 | Worldwide | 25,250,000 | AIDS | 1981 | |
| 9 | Worldwide | 12,000,000 | Bubonic Plague: Third Pandemic | 1850 | |
| 10 | Roman Empire | 5,000,000 | Antonine Plague | 165 | |