The native peoples had been ravaged for some time by disastrous epidemics sparing no tribe that came into contact with Europeans. Both the Iroquois and the Hurons were heavily afflicted. Apart from this scourge, however, the Iroquois had gained certain advantages over the Hurons. While most of the Iroquois rejected the missionaries, the Hurons ended up divided between those who became Christians under the influence of the Jesuits and those who remained loyal to their traditional beliefs. Furthermore, the Iroquois were very close to the Dutch in Fort Orange, with whom they traded, while the Hurons had to travel hundreds of kilometres to exchange their furs for French goods. Finally and most importantly from a military point of view, the Iroquois obtained firearms from the Dutch from approximately the year 1640, while the Hurons did not have any. Bolstered by all these advantages, the Iroquois felt that the time had come to implement their grand plan for the destruction of the Hurons, the allies of the French.
Perhaps because there was a scent of menace in the air, a detachment of eight soldiers from the Trois-Rivières garrison and four from the Montreal garrison escorted a large convoy of canoes headed for Huron country. These twelve soldiers carried with them a small piece of artillery for the defence of the Sainte-Marie mission.
The attack took place in the spring of 1649. More than 1,000 Iroquois warriors, armed to the teeth and outfitted with firearms, descended on Huronia. The final assault was under way after years of harassment. Several Huron villages, including the missions of Saint-Louis and Saint-Ignace, fell to the invaders. The losses were enormous. Only three of the 400 inhabitants of Teanaostaiae escaped with their lives, while the Iroquois lost only ten warriors. Other Hurons abandoned their villages, with no hope of returning, and scattered. Finally, the largest mission, that of Sainte-Marie, was abandoned, portending the end of Huronia. Its inhabitants, both French and Huron, took refuge on Christian Island, known as Gahoendoe in Amerindian. Here, in May 1649, with the help of able-bodied men, the few soldiers from the garrison transported the cannon that had arrived the previous year. They all applied themselves to constructing a little bastioned fort which they named Sainte-Marie II. However, famine struck the little colony of refugees during the winter of 1649-50, carrying off hundreds of Hurons. Finally, on June 10, 1650, after having buried not only their dead but also the cannon on the island, the approximately 300 surviving Hurons and the few remaining Frenchmen set out for Quebec, where they arrived on July 28. This was the end of Huronia, but not of the Hurons, for on October 15 of the same year, "the Hurons departed for war, " 
according to a note of the Jesuit superior in Quebec.