The 10 Worst Plagues, Epidemics, & Pandemics in History

The world today has been greatly affected by the recent pandemic. Throughout the course of history, disease has come and gone in waves of plagues, epidemics, and pandemics, with the results being catastrophic in some cases. Here you will find a list of the top 10 most catastrophic epidemics and pandemics caused by an infectious disease in history.

An epidemic of meningococcal infection is defined as an attack rate of more than 15 cases per 100,000 people in a population over a two-week period. There are many non-communicable diseases that are not included here, such as cardiovascular disease and cancer.

Since some plagues lasted for so long, they have been split by outbreak and characterized by the period where they took place. Read on to learn about every major pandemic, plague, and epidemic in recent human history in this 10 Worst Plagues, Epidemics, & Pandemics list; the statistics are mind blowing.

The List of the 10 Worst Plagues, Epidemics, & Pandemics in History

10. Russia Typhus Epidemic

Death Toll: 2-3 million

Years: 1918-1922
Location: Russia
Disease: Typhus
Population Loss: .1-.16%

The Russia Typhus Epidemic Explained

Typhus was a rampant problem in Poland and several other countries prior to World War I. During and shortly after the war, it caused up to three million deaths in Russia. Many troops, prisoners and even doctors were infected, and at least 150,000 died from typhus in Serbia.

During World War I and the Russian Civil War, the typhus epidemic ravaged the armies of the Eastern Front, causing 2-3 million deaths out of 20-30 million cases. Fatalities were generally between 10 and 40 percent of those infected, and the disease was a major cause of death for those nursing the sick. In response, delousing stations were established for troops on the Western Front.

North America and Western Europe have been able to prevent epidemics following the development of a vaccine during World War II. This continued research has set an improved disease control standard.

9. Mexico Smallpox Epidemic

Death Toll: 5-8 million

Years: 1519-1520
Location: Mexico
Disease: Smallpox
Population Loss: 1-2%

The Mexico Smallpox Epidemic Explained

Smallpox was brought to Mexico by those in Spanish ships, where it spread to the center of Mexico, and lead to the fall of Tenochtitlan. There were major epidemic outbreaks during the colonial period. This led to the implementation of sanitary and preventive policies to improve health conditions. Smallpox spans approximately 520 years of Mexican history, only being officially eradicated in 1951 with the introduction of a vaccine.

Prior to the arrival of the Europeans, smallpox was an unknown disease in all of the Americas. Hernán Cortés was sent to start trade relations only on the Veracruz Coast in 1519. Disobeying the Cuban governor, he invaded the mainland, so the governor sent Pánfilo de Narváez after Cortés. There was at least one active case of smallpox among Narvaez’s men, and the disease gained a foothold in the region in 1520.

The Mexico smallpox epidemic had a massive impact on the local population, with eye witness accounts claiming the very visible death toll.

8. Antonine Plague

Death Toll: 5-10 million

Years: 165-180
Location: Roman Empire
Disease: Smallpox or Measles
Population Loss: 3-6%

The Antonine Plague Explained

The Antonine Plague, also known as the Plague of Galen, was a pandemic that impacted the Roman Empire from 165 to 180 AD. It is believed that the plague was contracted and spread by soldiers who were returning from campaigns in the Near East. Scholars generally believe that the plague was smallpox, although measles has also been suggested.

The Roman emperor Lucius Verus may have succumbed to the plague in 169 AD. This event occurred during his co-regency with Marcus Aurelius. The two emperors had attained their positions by virtue of being adopted by the previous emperor, Antoninus Pius. As a result, their family name, Antoninus, has become associated with the pandemic.

It is generally agreed upon that the plague likely appeared during the Roman siege of the Mesopotamian city of Seleucia in 165. The plague spread to Gaul and to the legions along the Rhine, with a large proportion of the empire’s population dying from this outbreak. Nine years later, in 189 AD, the disease broke out again, this time causing up to 2,000 deaths a day in Rome. The total death count has been estimated at 5-10 million, which is roughly 10 percent of the population of the empire. The disease was particularly deadly in the cities and in the Roman army.

Read More Fun Facts

Learn more fun facts with Trivia Mastermind content.

7. Cocoliztli Epidemic

Death Toll: 5-15 million

Years: 1545–1548
Location: Mexico
Disease: Cocoliztli
Population Loss: 1-3%

The Cocoliztli Epidemic Explained

The Cocoliztli Epidemic, also known as the great pestilence, was a devastating event in which millions of people in present-day Mexico died from a mysterious illness called cocoliztli. This illness was characterized by high fevers and bleeding, and it left the people of New Spain reeling for years to come.

This outbreak is often referred to as the worst disease epidemic in the history of Mexico, based on the death toll. There has been little consensus among modern researchers on the pathogenesis of this disease and subsequent outbreaks continued to baffle doctors.

Recent bacterial genomic studies have suggested that Salmonella was at least partially responsible for this initial outbreak. Some speculate that it may have also been an indigenous viral hemorrhagic fever, in combination with droughts, as-well-as the Spanish conquest.

6. Third Plague Pandemic

Death Toll: 12-15 million

Years: 1855-1960
Location: Worldwide
Disease: Bubonic Plague
Population Loss: 30-50%

The Third Plague Pandemic Explained

The third pandemic of bubonic plague was one of the deadliest in history, killing more than 12 million people in China and India. It began in Yunnan, China in 1855 during the fifth year of the Xianfeng Emperor’s reign. The plague spread to all inhabited continents, causing widespread death and destruction. The pandemic was considered active until 1960, according to the World Health Organization.

Casualty patterns suggest that there may have been two different sources for this late-19th-century/early-20th-century pandemic. The first was primarily bubonic and was spread around the world through ocean-going trade and by infected persons, rats, and cargoes harboring fleas. The second, more virulent strain, was primarily pneumonic and highly contagious between people. This strain was largely confined to Asia, specifically Manchuria and Mongolia.

As the name references, this was the third major bubonic plague outbreak to affect European society. The first being the Plague of Justinian and the second being the black death.

5. COVID-19 Pandemic

Death Toll: 6.2-24.3 million

Years: 2019-present
Location: Worldwide
Disease: Covid-19
Population Loss: ~1%

The COVID-19 Pandemic Explained

The global pandemic of COVID-19, caused by the novel coronavirus SARS-CoV-2, first identified in an outbreak in Wuhan, China in December 2019, continued to spread worldwide despite attempts to contain it. The World Health Organization (WHO) had declared a Public Health Emergency of International Concern as of January 30, 2020 and a pandemic on March 11, 2020. The pandemic has caused more than 509 million cases and 6.21 million deaths, making it one of the deadliest in history.

Since December 2020, COVID-19 vaccines have been approved and widely distributed in various countries. Treatments have included symptom control, novel antiviral drugs, and monoclonal antibodies. Preventative measures include masking, improving ventilation and air filtration, social distancing, and quarantining those who have been exposed. Travel restrictions, lockdowns, business restrictions and school closures have been implemented by local governments to slow down the spread of the virus.

The pandemic triggered severe social and economic disruption globally. Widespread supply shortages of all kinds were caused by panic buying and disruption to the supply chain. A positive result of the lockdown was an unprecedented pollution decrease. Educational institutions and public areas were partially or fully closed in many areas, with many events postponed and canceled.

Play Trivia!

Challenge yourself and play trivia questions with answers and explanations.

4. HIV/AIDS Global Epidemic

Death Toll: 36.3 million

Years: 1981-present
Location: Worldwide
Disease: HIV/AIDS
Population Loss: ~1.5%

The HIV/AIDS Global Epidemic Explained

The HIV/AIDS Global Epidemic began in 1981, and is an ongoing worldwide public health issue. The World Health Organization (WHO) reports that, as of 2021, HIV/AIDS has killed approximately 36.3 million people and infected 37.7 million globally. Of these 37.7 million people, 73% have access to antiretroviral treatment, and 16% are unaware of their infection.

The number of deaths from HIV/AIDS has been declining in recent years, with an estimated 770,000 deaths in 2018 and 680,000 in 2020. This progress is largely due to decreases in incidence of HIV infection, which peaked in 1997 at 3.3 million per year but has fallen rapidly since then. As of 2020, there are approximately 1.5 million new infections of HIV per year globally.

The HIV epidemic has had a profound impact on sub-Saharan Africa, where 61% of new infections occurred in 2018. As of 2020, more than two thirds of those living with HIV are living in Africa. However, HIV rates have been decreasing in the region, with new infections in eastern and southern Africa falling by 38% from 2010 to 2020. South Africa remains the country with the largest population of people living with HIV, at 7.06 million, or 19.1% of the population as of 2020.

3. Plague of Justinian

Death Toll: 15-100 million

Years: 541-549
Location: Europe, Asia & Africa
Disease: Bubonic Plague
Population Loss: 7-56%

The Plague of Justinian Explained

The plague of Justinian or Justinianic plague was the first major outbreak of the first plague pandemic from 541–549 AD. The devastating disease spread like wildfire throughout the Mediterranean Basin, Europe, and the Near East, wreaking havoc on the Sasanian Empire and the Byzantine Empire – with Constantinople bearing the brunt of the destruction.

The plague, named for the Byzantine Emperor Justinian I (r. 527–565), was contracted by the emperor himself according to his court historian Procopius. The epidemic killed about a fifth of the population in the imperial capital, but Justinian recovered in 542. The contagion arrived in Roman Egypt in 541 and spread around the Mediterranean Sea until 544, before finally dissipating in Northern Europe and the Arabian Peninsula by 549.

The Justinian plague, which struck in the 6th century, was caused by Yersinia pestis, the same bacterium responsible for the Black Death centuries later. This was confirmed by researchers in 2013, who found that modern strains of Yersinia pestis are closely related to the strain that caused the Justinian plague. This suggests that the Justinian plague originated in or near the Tian Shan mountain range, on the borders of Kyrgyzstan, Kazakhstan, and China.

2. Spanish Flu

Death Toll: 17-100 million

Years: 1918-1920
Location: Worldwide
Disease: Influenza A/H1N1
Population Loss: 1-5.4%

The Spanish Flu Explained

The 1918 influenza pandemic, often called Spanish flu or the Great Influenza epidemic, was a deadly global influenza pandemic caused by the H1N1 influenza A virus.

The first documented case of the Spanish Flu was in March 1918 in Kansas, United States. However, further cases were recorded in France, Germany and the United Kingdom in April. Just two years later, it is estimated that nearly a third of the global population, or 500 million people, had been infected in four successive waves. Estimates of deaths range from 17 million to 50 million, and possibly as high as 100 million, making it the second deadliest pandemic in human history after the Black Death bubonic plague.

The outbreak of the Spanish flu pandemic near the end of World War I was initially reported in neutral Spain, leading to the misnomer “Spanish flu”. However, it is now believed that the pandemic originated elsewhere and was brought to Spain by infected soldiers.

1. Black Death

Death Toll: 75-200 million

Years: (1346-1353)
Location: Europe, Asia & Africa
Disease: Bubonic Plague
Population Loss: 17-54%

The Black Death Explained

The Black Death was a pandemic that devastated Afro-Eurasia in the 14th century. Also known as the Pestilence, the Great Mortality, or the Plague, the Black Death killed an estimated 75 to 200 million people, making it one of the deadliest pandemics in human history.

Bubonic plague is caused by the bacterium Yersinia pestis, which is spread by fleas. It can also take a secondary form where it is spread person-to-person contact. This is created via aerosols causing septicaemic or pneumonic plagues.

The Black Death was the beginning of the second plague pandemic. The plague was a devastating event that forever changed European history. The cause of the Black Death is disputed. Some say it originated in Central Asia or East Asia, while its first definitive appearance was in Crimea in 1347. Others believe it was carried by fleas living on black rats that travelled on Genoese ships, spreading through the Mediterranean Basin and reaching Africa, Western Asia and the rest of Europe via Constantinople, Sicily and the Italian Peninsula.

Read More Fun Facts

Learn more fun facts with Trivia Mastermind content.

Play Trivia!

Challenge yourself and play trivia questions with answers and explanations.

Trivia Mastermind Editorial Team

We are fact fanatics, writers, and most importantly, trivia enthusiasts. We have spent thousands of hours creating original trivia questions and fun fact articles for your enjoyment. There are currently, over 6,250 trivia questions on for you to check out. We hope you love them!

Recent Posts