1600
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It's impossible to pinpoint the specific factors of why the year 1600 marked the start of one of the worst periods in human history because there are so little historical documents from that period to go on. It was the Little Ice Age, which began in 1600 with the eruption of the volcano Huaynaputina in Peru, while current research points to a major population decline following the arrival of Europeans in the New World as another possible explanation. It caused unusually cold weather in numerous parts of the world, including China, Korea, Japan, practically all of Europe, and parts of Africa and the Americas. Unlike many of the other periods on this list, this one spanned practically the whole known world and lasted decades, producing massive societal upheaval and suffering.
This worldwide temperature drop would serve as the foundation for all of the world's catastrophic events in the 17th century. It resulted in a severe drop in summer temperatures in China, causing widespread crop failure and illnesses throughout the country. This would eventually lead to the Ming dynasty's demise in 1644 as a result of a peasant insurrection spurred in large part by widespread food scarcity and social unrest. The similar thing occurred in other places of Asia. In 1670, for example, a drought killed 20% of Korea's population.
There were frosts in Europe during the summer months virtually the entire century, resulting in rebellions, infectious disease outbreaks, and famine, which eventually translated into war and societal upheaval not witnessed in the relatively wealthy years of the previous several decades. According to some records, civil conflict and famine in Ireland claimed over 500,000 lives over the course of about a decade in the 1650s.
This was also the century of Europe's Thirty Years' War, one of the most terrible religious confrontations in human history, which was directly fueled by the starvation and extreme temperatures of the ice age. While there are too many long-term repercussions to list here, estimates imply that the diseases, conflicts, famines, and civil wars produced by this global cooling event killed roughly one-third of the known global population at the time.