Brûlé travelled to New France in 1608. He became a sort of 'exchange student' when he was sent by Samuel de Champlain to live with the Hurons in 1610 and Champlain in turn accepted the company of a Huron youth named Savignon. He traveled with the Huron and their chief (Iroquet) to the shores of southern Georgian Bay. There he spent a year in their village, learned their language and customs. He became a scout for Champlain and explored much of what is now Quebec, Ontario, and Michigan.
He was probably the first European to see all the great lakes Lake Huron, Lake Ontario, Lake Erie, Lake Michigan and Lake Superior, and one of the first Europeans to set foot in the future states of Pennsylvania and Michigan. He travelled widely going as far south as the Chesapeake Bay, and as far west as the site of Duluth, Minnesota. On the way back to Quebec, he was briefly captured and tortured by the Iroquois.
Champlain and the Jesuits often spoke out against Brûlé's adoption of Huron customs, as well as his association with the fur traders, who were beyond the control of the colonial government. Brûlé left Quebec to live with the natives in the 1620s and became the first European to travel up what would be named the St. Marys River and into Lake Superior. Brûlé was later confined in Québec for a year, where he taught the Jesuits the natives' language, and was then sent back to Europe and prohibited from coming back to New France. Brûlé then set out for England and helped English capture Champlain and Quebec City in 1629 (though the colony was returned to France in 1632).
Brûlé continued to live with the natives, acting as an interpreter in their dealings with the French traders. Though the circumstances of his death are unclear and many different versions circulate about the reasons, it is most thought that he was captured by the Seneca Iroquois in battle and left for dead by his Huron group. He managed to escape death by torture, but when he returned home the Hurons did not believe his story and suspected him of trading with the Senecas. Treated as an enemy, he was consequently tortured to death by his allies. He died at Toanche and was buried by the Hurons, who interred only those who met death by violence.