Tribes as political entities or ethnolinguistic groups as political entities is a concept that does not work for a large part of western North America as I discuss here. The social organization of western North American natives was, in large part, organized at the level of extended family or household.

In eastern North America, particularly in the eastern woodlands, Polities (Chiefdoms) that extended over a considerable geographic range developed in the mid to late Mississippian period 1200-1600 CE. Even though these chiefdoms might cover an area of 10 miles square to 25 miles square (Edit:see /u/Reedstilt comments below. He provides useful and more accurate information than mine with regard to Chiefdom size and organization.), they were limited in size by the absence of specialized political organization supporting the Chiefs. Chiefs lacked specialized administrative personnel to manage larger groups.

In Mesoamerica, city states developed in late prehistory that supported perhaps 100,000 people.

The answer to your question is no, there was never a time, that we know of, in prehistory that natives of a large portion of the continent were organized in just a few political entities/tribes.

With regard to when the continent was most unified, it is likely in the very late prehistoric/contact period either when many large chiefdoms prevailed in the eastern woodlands or when the city states of Latin America developed. However, none of these political entities dominated "a large portion of the Continent".

From the Pleistocene to the Holocene: Human Organization and Cultural Transformations in Prehistoric North America C. Britt Bousman; Bradley J. Vierra Texas A&M University Press, 2012

Prehistory of North America Mark Sutton, Routledge, 2015

Mound Sites of the Ancient South: A Guide to the Mississippian Chiefdoms Eric E. Bowne, Univ. of Georgia Press, 2013