The disease that has killed the most people ever in history is the disease Smallpox.
The disease Smallpox which is known as a Pandemic disease smallpox throughout history, has killed between 300 500 million people in its 12,000 year existence.
Yes Smallpox has existed for over 12,000 years and has killed a bunch of people and it was and still is a very deadly disease.
But Smallpox was even more deadly many years ago before all the advances in medicine and knowledge that the doctors have today.