Per a Quora question about the most important single issue in "American" history, the header says what this is about.

Imagine a "New World" that would indeed be new by, as well as for, Euro-Americans because nobody came here from Siberia 20,000 or more years ago.

Think of how different the New World is with no pre-European population. (I’m setting aside whether or not Polynesians sailed to South America; if they did, it seems unlikely they left permanent genetic descent, and besides possibly bringing the sweet potato [history still disputed], left little cultural descent.)

First, a bunch of charismatic megafauna would have stayed alive, such as larger-sized bison, Columbian mammoth, New World camels and maybe even saber-toothed cats, among others.

Now, humans.

Erik the Red left Greenland mainly because of the end of the Medieval Warm Period, but early Inuit helped speed him along. Would he have stayed otherwise? Maybe.

Leif was sped off by people who were likely Algonquin-speaking Indians as well as climate, just like Erik, plus being that much further from Europe and European supplies. (As far as we can tell, neither Norse settlement made their own iron.)

Probably climate would have driven both away.

So, Columbus would have come to an unpopulated world. Without the help of Caribbean natives, he would have found no gold.

Would he have made a second trip? Unlikely.

So, next? Pedro Cabral gets blown off course just as in reality. Do the Portuguese stay with no American Indians? If so, do the Spanish follow? Are the French and English then likely to follow?

With no easy New World gold or silver and nobody to tell them where to look, no natives to enslave, and less reason to enslave Africans, the New World is populated and developed but slowly.

And, without American Indian crops? No corn, tomatoes, chiles or potatoes, among other things, in the Old World. No Irish peasantry because of no potatoes. Etc. etc.