Final answer:
The most significant change in North America before European contact occurred with the introduction of European diseases, starting in 1492, leading to devastating population losses among Indigenous peoples. Over 500 diverse groups existed in North America pre-contact, with commonalities within regions.
Step-by-step explanation:
The greatest and most sudden change in North America and the Southeast before European contact happened during the periods of initial European exploration and colonization, which began in earnest with Columbus's voyage in 1492. The most profound impact was the introduction of diseases to which the Indigenous peoples had no immunity, leading to catastrophic mortality rates. For instance, between 1616 and 1618, epidemics claimed the lives of 75 percent of the native people along the New England coast. Similarly, in the 1630s, half the Huron and Iroquois around the Great Lakes died of smallpox. This resulted in the loss of entire generations and the irreplaceable knowledge and traditions they held.
Prior to these events, the pre-contact era in North America saw the emergence of over 500 identifiable groups. These groups, while distinct, shared commonalities within their respective regions in terms of subsistence strategies, kinship relations, political structure, and material culture. The advent of European colonialism not only wrought havoc with diseases but also initiated the Columbian Exchange, profoundly altering the demographic, ecological and cultural landscapes of both European nations and the Americas.