50,000 - 12,000 B.C. – No one is quite certain as to when Asians first migrated to North America. These dates represent the extreme earliest possible date of entry and the extreme latest possible date of migration. Perhaps as early as 8,000 B.C. the migration had reached the southern tip of South America. Estimates range as to the population of the Americas in the late fifteenth century, when the first important contact was made with Europeans. Some scholars believe that as many as 100 million people lived in Central and South America at this time, while others believe about10 million dwelled in those areas. Population estimates for North America, above Mexico, are less extreme, with estimates ranging from 4 to 10 million. In 1492, some estimates state that the population of Hispaniola, the island where Columbus landed, was home to between 7 and 8 million inhabitants – a population roughly equivalent to that of Spain at the time. This estimate too varies, with a low of about one million.

1001 A.D. – Leif Ericsson establishes a settlement in Newfoundland, but word of the settlement, which he called Vinland, never reaches Europe and he soon abandons the site.

1275 - 1295 – Marco Polo travels to China from Italy. The exotic goods with which he returned inspired voyages of exploration, as merchants were anxious to find a faster, safer route to the Orient. Accounts of Marco Polo's travels were not published until 1477, more than 150 years after his death, but at a time when navigational skills and technology had improved to the point that exploring a sea route to the Orient became a possibility.

c. 1300 – Rise of the Aztec empire. The Aztecs, who invaded central America, built on the achievements of the Mayas, who had built cities with palaces, bridges, aqueducts, baths, astronomical observatories, and temples topped by pyramids. Mayan priests developed a written language; their mathematicians discovered the zero, and their astronomers devised a calendar more accurate than any other then in existence. During the 1300s, the Aztecs created an empire of several million people with a capital city, Tenochtitlán (current-day Mexico City), which featured the Great Temple of the Sun in its center. Through canals, the thriving capital transported gold, silver, exotic feathers, cocoa, and millions of pounds of maize. While the Aztecs conquered other peoples primarily to obtain slaves, human sacrifices (thousands would be killed annually when priests sliced open chests to offer the sun god a still-beating heart), and wealth, and while they developed an elaborate administrative, educational, and medical system comparable to the most advanced in Europe at the time, they did not force conquered city-states to take their language and customs nor did they station their people in conquered areas. Yet these conquered areas bitterly resented Aztec rule. Thus by the arrival of the Europeans around 1500, the Aztec empire found itself vulnerable to division within and attack from abroad.

1347 – First outbreak of the Black Death, a catastrophic epidemic of the bubonic plague, wipes out perhaps as much as half of the population of Europe.

1492 – Columbus discovers America. Commanding ninety men and three ships (the Niña, the Pinta, and the Santa Maria), Columbus left Spain in August and on October 12 set anchor on the island he called San Salvador. He assumed he had reached an island off Asia.

1497 – John Cabot (born in Genoa as Giovanni Caboto) explores North America under the sponsorship of King Henry VII. Cabot discovered Newfoundland and told of the tall trees that could be used in ship building and of the plentiful codfish off the island's coast. In 1498 Cabot set sail to search for a Northwest Passage to Asia; he and his five ships were never heard from again.

1517 – The Protestant Reformation begins in Germany when Martin Luther posts his 95 theses challenging basic practices and beliefs of the Catholic Church. Luther, a Catholic priest, was excommunicated, but the influence of his theses spread rapidly throughout Europe. He believed that every individual should read and interpret the Bible for himself and that human nature was innately evil; he himself despaired of leading a life that gained salvation. Salvation, he argued, was a "free gift" from God to undeserving sinners. The ability to live a good life could not be the cause of salvation but its consequence, once individuals believed they had been granted saving faith. Luther's ideas greatly influenced the Puritans.

1518 - 1530 – Smallpox decimates Indian populations. Native Americans were tragically vulnerable to such illnesses as influenza, measles, typhus, and above all, smallpox – diseases Europeans had, over time, developed at least a partial immunity. Populations were virtually wiped out. On Hispaniola (Domincan Republic and Cuba), where Columbus established a colony, perhaps millions of Native Americans were destroyed, so that within a few decades, the Native American population fell to 500. In the Mayan areas of Mexico, as much as 95% of the population was destroyed within a few years of the natives' contact with the Spanish.

1519 - 1522 – Ferdinand Magellan, a Portuguese sailing under the Spanish flag, conducts the first expedition to circumnavigate the globe. Magellan himself died in a conflict with the natives in the Philippines in 1521, but his sailors completed the circumnavigation.

1521 – Tenochtitlán surrenders to Cortés after a siege of eighty-five days. The Spanish conquistadors, by just about all accounts, were brutal and greedy. They conquered the sophisticated Aztec empire and later, under the Pizarro brothers, conquered the Incas, The Spaniards took advantage of superior technology, the edge of surprise, disease, and political disunity in the Indian empires. The sight of ships, the explosion of guns, men on horseback (whom the Indians first thought a single creature), terrified the Indians. In addition, the conquistadors found eager allies among resentful tribes ruled by the Aztecs and Incas.

1524 – Giovanni da Verrazzano explores the eastern coast of the present-day United States, discovering the mouth of the Hudson River.

1528 – Alvar Núñez Cabeza de Vaca arrives in Tampa Bay under an ill-fated expedition led by Pánfilo de Narváez. Cabeza de Vaca would later write about his eight-year life among Indian tribes.

1550s – Conquistadors, led by the Pizarro brothers, sail along South America's Pacific coast and conquer the Incas in Peru, a civilization as impressive as the Aztecs, and claim Ecuador, Chile, Argentina, and Bolivia for Spain. The conquistadors, it should be noted, resented the Spanish monarchy and had hoped to establish themselves as a colonial nobility independent of Spain. The monarchy did not allow their idea to take root, and sent imperial officials to rule the colonies.

1558 – Elizabeth I becomes queen of England.

1565 – St. Augustine, Florida founded. The modest Spanish fort of St. Augustine represents the first permanent settlement in the present-day United States. The settlement was little more than an outpost and headquarters for unsuccessful missionary campaigns.

1576 - 1578 – Martin Frobisher's search for a Northwest Passage to Asia is unsuccessful. He returns to England with an Eskimo, whom he took with kayak right from the Atlantic Ocean, and a large black stone, which he futilely hoped would be gold ore.

1584 - 1590 – The English attempt to establish a colony on the island of Roanoke. With Queen Elizabeth's support, Sir Walter Raleigh sent a small group of men on an expedition to explore the North American coast. After their return, Raleigh named the area they explored Virginia, after Elizabeth, who was unmarried and called the "Virgin Queen." An attempt to establish a settlement first failed in 1586 after conflicts with the Indians. Frustrated and dispirited colonists abandoned the island. Raleigh was undeterred and tried again in 1587. John White was appointed governor, but upon arrival fighting again broke out with local Indians. Seeking reinforcements, White returned to England on the ship that brought him. However, by the time he arrived home, England was at war with Spain, and White had to put off his return to Roanoke for three years. When he landed on the island next in 1590, he found Roanoke deserted. There was no clue as to the fate of the settlers except for the cryptic inscription "Croatian" carved on a post. The mystery of the "Lost Colony" has never been solved. (See John White's painting, Natives of Roanoke Island, in the center section.)

1588 – The English defeat the mighty Spanish Armada as it sails to attack England. The smaller English fleet was able to outmaneuver the much larger Spanish fleet. The English victory ended Spain's domination of the Atlantic Ocean and its threat to English colonization in the New World.

late 1500s – Powhatan overcomes many difficulties to form an Indian confederacy numbering over 9,000.