The 8 Deadliest Diseases in Human History

The 8 Deadliest Diseases in Human History

The 8 Deadliest Diseases in Human History

Key Points

  • COVID-19 is one of the deadliest diseases in human history, causing monumental divides between people in every country.
  • HIV/AIDS was once a death sentence but is now manageable and no longer an imminent threat.
  • Typhus continues to be a deadly disease, primarily affecting people in third-world countries with limited access to medical facilities.
  • The flu, including the Spanish Influenza, has historically caused millions of deaths worldwide.
  • Cholera is an insidious disease transmitted through unsanitary water and food, prevalent in areas with poor infrastructure.
  • Smallpox, once a devastating disease, has been eradicated through vaccines.
  • Ebola has a high mortality rate and is greatly feared due to its potential to mutate.
  • The Black Death, caused by the Yersinia Pestis bacteria, killed a significant portion of the population and had long-lasting effects on society.

In light of the COVID-19 pandemic, a conversation about the deadliest diseases in human history seems macabre. But history is nothing if not cyclical. What came before will come again, even if the underlying reasoning is nothing more than time and odds.

In many ways, diseases are less fearsome today, mostly because, if nothing else, information is constantly flooding in. We have to sift through good and bad information, sure, but hundreds, even thousands of years ago, humanity had no such recourse.

The diseases that swept through humanity did so with a limited understanding of the disease, what it meant, or where it came from. These diseases were only limited by their ability to spread and, ultimately, to kill.

After that light-hearted introduction, let’s discuss the 8 deadliest diseases in no particular order.

#1: COVID-19

Time PeriodNumber of Deaths
2019 – Present7 million+

The 7 million figure is simply a World Health Organization (WHO) confirmed number of cases, though the organization also includes 15 million likely deaths between 2020 and 2021, associated directly or indirectly with COVID-19.

One thing is certain, COVID-19 is alive and well across the world and we are all still dealing with it in one way or another. It’s also one of the most political diseases in history, causing monumental divides between people in every country. It’s a distinct feature that separates COVID-19 from every other disease and makes it historically unique.

While there is little doubt that COVID-19 is one of the deadliest diseases in human history, much about the disease has proven controversial, with even scientists arguing over its deadliness and source. Considering the politically charged environment we live in, that’s not likely to change anytime soon.

coronavirus covid-19
COVID-19 is still very much alive and well today, with recent spikes reported in different areas around the world.

©HFCM Communicatie / Creative Commons Attribution-Share Alike 4.0 International license – License


Time PeriodNumber of Deaths
1981 – Present35 million+

When HIV showed up in the late 70s and early 80s, no one knew what it was — only that it emaciated the immune system and there was almost zero chance of survivability. The insidious nature of the disease made it one of the most terrifying in the modern era.

Today, the disease is manageable and no longer an imminent death threat. If you can imagine being diagnosed with HIV in the 80s and 90s, it was a death sentence. Even with cancer, there is at least the hope of remission.

Fortunately, major advancements in the way we treat HIV make it manageable and nearly negligible. Only third-world countries still feel the fear of HIV and even those countries are making progress in repressing and managing the disease.

HIV/AIDS gluten comparative virus
The HIV virus is 16x the size of a toxic fraction of gluten.

©BallenaBlanca / Creative Commons Attribution-Share Alike 4.0 International license – License

#3: Typhus

Time PeriodNumber of Deaths
1489 – 19223,402,000

Typhus is one of the deadliest diseases in human history because it never seems to completely go away. Even today, one in every 5 million people dies of typhus every year all across the world. Deaths mostly occur in third-world countries where people have limited access (if any) to medical facilities and treatment.

Typhus is historically a thorn in Russia’s side, having struck twice since 1489 — both times devastating the population but even more so during the Russian typhus epidemic that lasted four years from 1918 to 1922.

Its primarily spread by lice and fleas, which tend to crop up in unsanitary conditions. Doxycycline is the antibiotic of choice for treating Typhus today. But again, it’s not readily available in many areas throughout the world. For the most part, typhus presents itself as the flu with headaches and fever. It often causes a rash as well.

typhus epidemic macular rash
Typhus is still a concern in countries around the world.

©Georg Jochmann / Creative Commons Attribution-Share Alike 4.0 International license – License

#4: Flu

Time PeriodNumber of Deaths
1510 – PresentMillions

The impact of the flu is often minimized. The term is used to casually describe any number of flu-like diseases. It’s common to hear sick people proclaim they have the flu. In reality, the flu is devastating and likely to render even the healthiest of us bedridden for a couple of days.

The flu is like the cold with a wide variety of strains existing over the centuries. Perhaps the most well-known flu, historically speaking, was the Spanish Influenza, which has to historically be the worst-timed major disease ever. It struck at the tail end of World War I, lasting from 1918 to 1920 and killing anywhere between 15 million and 100 million people worldwide.

The worst part about the Spanish Flu is its similarity to the regular flu except it never ends, progressively worsening until death follows. The Asian Flu was nearly as brutal, followed by the Hong Kong Flu and the Russian Flu.

stop the flu in its tracks flu prevention
With annual flu vaccines, the prevalence of the disease and the seriousness of its symptoms can be better managed.

©Metropolitan Transportation Authority of the State of New York from United States of America / Creative Commons Attribution 2.0 Generic license – License

#5: Cholera

Time PeriodNumber of Deaths
1817 – PresentApprox. 2,943,563

Not only is cholera one of the deadliest diseases in human history, but it’s also a particularly insidious disease. It attacks the small intestine, killing the host by way of dehydration. Once the disease takes hold, explosive vomiting, diarrhea, severe abdominal cramps, and dehydration result.

It’s quite literally the world’s nastiest case of food poisoning. In fact, the disease is mostly transmitted through unsanitary water and food — mostly the former. A cholera infection was first recorded in 1817, though we suspect the disease is far older — many centuries older.

Cholera is still prevalent in areas around the world where unsanitary living conditions are common. Since the disease typically makes its way from human waste into water and food supplies, poorer countries with limited or decaying infrastructure are often hit hardest. The most recent cholera outbreak took place in Yemen (2016–2021), killing nearly 4,000 people.

disposal of dead bodies cholera epidemic
The most recent cholera outbreak was in Yemen, between 2016 and 2021.

©Welcome Images / Creative Commons Attribution 4.0 International license – License

#6: Smallpox

Time PeriodNumber of Deaths
1735 – 1974Millions

Variola major and variola minor are the two types of the smallpox virus, and the disease certainly qualifies as an ancient one. Despite its history, over the many, many centuries, smallpox is most infamously known for wreaking havoc in the 18th and 19th centuries.

Both centuries saw millions succumb to the ravages of the disease, which include the well-known spots that raise up on the skin, accompanied by a fever, vomiting, and fluid later filling up the bumps. Oftentimes, even survival was its own nightmare, with the disease leaving the “lucky” ones blind or severely scarred.

Fortunately, vaccines turned the disease into a terrifying tale that only exists in the past. The last known smallpox outbreak of any significance occurred in the 1970s.

6. Smallpox
Smallpox is certainly not any small, inconsequential disease.

#7: Ebola

Time PeriodNumber of Deaths
1976 – Present15,266

Ebola is often left off the list when discussing deadly diseases, historically and presently. That’s probably because the death count for the disease is comparatively so low.

The fact is, for every two people ebola infects, one will die. The disease has a 50% mortality rate, making it easily one of the deadliest diseases in human history. Symptoms of the disease are excessive and brutal, including bleeding from various orifices, vomiting, muscle cramps, severe headaches, severe diarrhea, bruising, and death.

It’s no doubt one of the most punishing diseases in existence, and it’s still greatly feared throughout Africa and among doctors and scientists. They fear it because of the potential for such a brutal disease to mutate, making it easier to pass on from an infected person to a non-infected person.

ebola virus graphic
The Ebola virus is one of great concern, with a 50% mortality rate.

©CDC Global / Creative Commons Attribution 2.0 Generic license – License

#8. Black Death/Bubonic Plague/Plague of Justinian

Time PeriodNumber of Deaths
541 – 1912 (some present-day cases)75 – 200 million

The deadliest plague in human history is the Black Death, otherwise known as Bubonic Plague and originally as the Plague of Justinian or Justinian’s Plague. The Black Death is the source of countless books, articles, and documentaries. It’s also an endless source of fascination for historians and scientists alike.

The Black Death is caused by the Yersinia Pestis bacteria and it primarily transmits via fleas. Of course, they didn’t know that throughout the most devastating years of the plague. Some estimations have the plague killing 60% of the known population at the time, sometimes leaving entire towns and cities desolate.

Not only did it kill, its after-effects continued the deadly scourge. With fewer people to work the farmland, large swathes of the countryside went unharvested, leading to the starvation and deaths of countless more. The Black Death was one of the most devastating diseases to ever wreak havoc on humankind and will remain an endless source of fascination for amateur and professional historians alike.

black death bubonic plague
The Bubonic Plague is the most deadly disease in history, claiming up to 200 million lives.

©Welcome Images / Creative Commons Attribution 4.0 International license – License

Final Thoughts

All of the deadliest diseases on this list are relatively well-known to most people. That’s because their history is frightening and devastating, mostly on a worldwide scale. COVID-19 may not be the deadliest, but the fact that it’s a recent pandemic cements it in the mind more thoroughly than any historical retelling.

Worse, COVID-19 likely won’t be the last disease to panic the planet, destroy industries, and kill millions. The deadly disease is cyclical and humankind goes on by developing immunity and harvesting the power of science in a never-ending effort to battle against a formidable foe that is ever-changing.

Nobody knows when the next one will arrive. Hopefully, long after everyone reading this and many generations after are long gone!

Summary Table

DiseaseYears ActiveEstimated Deaths
COVID-192019 – Present7 million+
HIV/AIDS1981 – Present35 million+
Typhus1489 – 19223,402,000
Flu1510 – PresentMillions
Cholera1817 – PresentApprox. 2,943,563
Smallpox1735 – 1974Millions
Ebola1976 – Present15,266
Black Death/Bubonic Plague/Plague of Justinian541 – 1912 (some present-day cases)75 – 200 million

Frequently Asked Questions

What is the most deadly disease in human history?

The most deadly disease in human history is the Bubonic Plague, otherwise known as the Black Death, which killed anywhere between 75 million and 200 million people.

What is the number one disease in America?

Heart disease is the number one killer in America today.

What disease has the lowest survival rate?

Rabies is the disease with the lowest survival rate, despite being well-known for centuries. It is nearly 100% fatal.

What is the rarest deadly disease?

The rarest deadly disease is RPI Deficiency, which is a critical, Ribose-5-Phosphate Isomerase enzyme in the human body. Those with the disease do not produce the enzyme naturally.

What is the most dangerous virus on earth?

The most dangerous virus on earth is the Marburg virus, which has a 90% fatality rate and is similar to Ebola.

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