Giovanni da Verrazzano landed in North Carolina in 1524, and was the first European to sail into New York Harbor and Narragansett Bay. Despite being Calvinists and building the Reformed Church in America, the Dutch were tolerant of other religions and cultures and traded with the Iroquois to the north. Another group, the Oshara tradition people, who lived from 5,500 BCE to 600 CE, were part of the Archaic Southwest. Jefferson, a scientist, supported expeditions to explore and map the new domain, most notably the Lewis and Clark Expedition. Britain never achieved the war goal of granting the Indians a barrier state to block further American settlement and this allowed settlers to pour into the Midwest without fear of a major threat.

As defined by Hine and Faragher, "frontier history tells the story of the creation and defense of communities, the use of the land, the development of markets, and the formation of states". Native American attacks continued, with the most significant occurring in the 1637 Pequot War and the 1675 King Philip's War. In the 1660s, the Middle Colonies of New York, New Jersey, and Delaware were established in the former Dutch New Netherland, and were characterized by a large degree of ethnic and religious diversity. However, London continued to regard the American colonies as existing for the benefit of the mother country in a policy known as mercantilism.A national debate took place over whether the constitution should be ratified, and it was ratified by a sufficient number of states in 1788 to begin forming a federal government. Mass dissatisfaction with corruption, inefficiency, and traditional politics stimulated the Progressive movement, from the 1890s to the 1920s, leading to reforms, including the federal income tax, direct election of Senators, granting of citizenship to many indigenous people, alcohol prohibition, and women's suffrage. New England became a center of commerce and industry due to the poor, mountainous soil making agriculture difficult. The central issue after 1848 was the expansion of slavery, with the anti-slavery elements in the North pitted against the pro-slavery elements that dominated the South.

This marked the rise of the Hawaiian civilization, which would be largely separated from the rest of the world until the arrival of the British 600 years later. At the same time, the Iroquois of New York, strengthened by years of fur trading with Europeans, formed the powerful Iroquois Confederacy. The Mexican–American War (1846–1848) broke out with the Whigs opposed to the war, and the Democrats supporting the war.The Republicans worried the decision could be used to expand slavery throughout all states and territories. The Pilgrims sailed for Virginia on the Mayflower in 1620, but were knocked off course by a storm and landed at Plymouth, where they agreed to a social contract of rules in the Mayflower Compact. Inspired by revolutionary ideals of the equality of men and influenced by their lesser economic reliance on slavery, northern states abolished slavery.