In the seventeenth and eighteenth centuries, the Renaissance would give way to the Age of Reason, also known as the Enlightenment. Technological developments such as moveable-type printing presses, allowed for the greater dissemination of knowledge as books became more available. This development, in turn, promoted a general thirst for knowledge and a belief in the power of science and reason.

Exposure to new cultures made possible by what became known as the Age of Discovery in the sixteenth century also promoted new ideas as European explorers and traders came into contact with cultures in Asia, Africa, and the Americas. This era of exploration had a dark side; mercantilism, the dominant economic theory of the early modern period, demanded that national policies be set according to considerations of international trade. In the pursuit of wealth, many wars were fought, and brutal policies—chief among them the slave trade in Africa and the genocide of the indigenous populations of the Americas—were endorsed and subsidized by European governments.

The slave trade had a profound effect on the continent of Africa. Between the early 1500s and the mid-1800s, somewhere between thirteen and twenty million Africans were enslaved. Some African kingdoms, such as the Kingdom of the Kongo in central Africa, were devastated by the slave trade, while other kingdoms such as the Kingdom of Dahomey and the Oyo Empire (a Yoruba kingdom) in west Africa benefited from trade with the Europeans.

The vast majority of African slaves were sent to the Americas to work on plantations and in mineral mines administered by European powers (primarily Spain and Portugal in Central and South America, and England and France in North America). Spain was the first of the European powers to establish colonies following the landing of explorer Christopher Columbus in 1492. The discovery of mineral wealth prompted a rush to colonize the territory. Early in the sixteenth century, Spanish conquistadors were able to topple the mighty Aztec and Inca empires in present-day Mexico and Peru, respectively, due to their superior weaponry and the weakening of the indigenous population through disease. The military effort was combined with a missionary zeal to convert the native populations to Christianity. The enslavement and subsequent brutal treatment of the indigenous peoples resulted in a mass depletion of the population.

The native populations of North America would be similarly devastated by European colonists as they succumbed to European diseases although they would not undergo mass enslavement. Instead, European colonists sought to overtake Native lands in order to make room for growing European settlements. These efforts led to frequent skirmishes between Europeans and Native Americans, although sometimes they fought together as allies. For example, different tribes took sides with either the French or the British during the French and Indian War (1754–1763). While Great Britain would emerge victorious in that conflict, it would later lose an important colony during the American Revolution (1775–1783), which would result in the formation of the United States.

While empires toppled under European encroachment in the Americas, empires thrived during the early modern period in the Middle East and Asia. The dominant empire in the Middle East, the Ottoman Empire, finished off the weakened Byzantine Empire by taking the city of Constantinople in 1453, an event that some historians mark as the beginning of the early modern era. The Ottomans expanded into the Mediterranean and North Africa in the sixteenth century. In the Islamic realm of Persia (present-day Iran), the Safavid Empire was founded in 1501 and became a rival to the Ottomans in the Middle East. While the Ottomans faced incursion from the Safavids from the east, they also had to contend with Europeans to the north; the defeat of its navy in the Battle of Lepanto in 1571 to a European coalition signaled the beginning of the mighty empire’s long decline. In Asia, the Qing dynasty overthrew the Ming Dynasty in China in 1644, and the Mughal Empire was founded in India in 1526; both of those empires would endure for the rest of the early modern period.