There are some errors in /u/dbcanuck's post, at least if we're thinking of the area prior to the arrival of Europeans. A lot of what's said in that post more closely resembles a later colonial era view. The main issue is that dbcanuck skips over the people who were living in the immediate Niagara area at the time.

At the time of European contact, or perhaps slightly before, the the Erie had been living east of the Niagara River, with the Seneca being east of them (the Genesee Valley being the boundary). In traditional Iroquoian history, the Erie were once part of the Seneca - and thus part of the Haudenosaunee (the Iroquois Confederacy). Eventually they opted for autonomy and left the Haudenosaunee to form their own confederacy; there are two versions of this story - one that says the split happened during a war and another that says the split was peaceful but a war followed sometime later. Regardless, this war is said to be the reason that the Erie Confederacy moved from the eastern Niagara region to the eastern shore of Lake Erie.

Their departure left the area between the Niagara River and the Genesee River virtually uninhabited. The Seneca were eyeing it for themselves, but so were the Wenro. The Wenro were one of the nations of the Chonnonton / Neutral Nation that existed in southern Ontario west of the Niagara River. Incidentally, the Niagara are one of the other nations in this group and river and falls were named after them. I wrote more about Chonnonton culture in this post.

The Wenro crossed the Niagara River in the late 1620s, thinking the rest of the Chonnonton would back them up if they needed to fight the Seneca. Seneca called their bluff, and the Chonnonton decided to cut the Wenro loose rather than fight the entirety of the Haudenosaunee. Since they were on their own, the Wenro decided to cede the territory to the Seneca and evacuated to the Wendat (Huron) Confederacy north of Lake Ontario. This map so the situation in 1630, just before the Wenro exodus (EDIT: I just notice that the map still has "St. Lawrence Iroquois" north of the Mohawk. This is inaccurate since the St. Lawrence Iroquoians lost a war against the Algonquins and ended up merging with the Wendat and the Mohawk. So in 1630, that area should be Algonquin.)