Unlike their Muskogean neighbors in the Southeastern woodlands of North America, the Cherokee spoke an Iroquoian language, their ancestors having traveled south long before Europeans arrived. There's precedent for the Iroquois Confederacy incorporating distant Iroquoian branches; after the southern Tuscarora were defeated in war, they traveled north and were folded back into the ranks of the Haudenosaunee. The Cherokee were one of the larger and more successful tribes, and stayed in the Southeast until they were forcibly removed along the Trail of Tears. By then, the Haudenosaunee was essentially gone, so in this TL they'd have to move earlier.
I'm thinking some POD in the Anglo-Cherokee war that puts Dragging Canoe in a greater position of power, and sooner; in the 1770s he convinces all the Cherokee to move north, rather than taking some west. In particular, I'm wondering if additional Cherokee population, as well as their literacy rates, legal systems, and so on, would have been helpful in securing Iroquois control over the future Northwest Territory, which they often had some form of legal claim over, but in practice were never able to settle. On the other hand, I'm not sure a nation as large and organized as the Cherokee would be welcomed by the decentralized Confederacy.