He entered a Jesuit novitiate as a boy but later left the religious life. In 1666 he went to Canada, where he developed a seigniory at Lachine. In 1673 the governor of New France, Frontenac, made him commandant of Fort Frontenac (see Kingston, Ont., Canada). After a visit to France, where he was granted a patent of nobility, La Salle began (1675) to develop the trade at the post. In 1677 he was in France again and obtained a patent to build forts, explore, and trade. When he returned, he brought with him Henri de Tonti, who was his lieutenant in later enterprises.
In 1679 a blockhouse was built at the outlet of the Niagara River, and in August they set out across the Great Lakes in the Griffon, which Tonti had built. That first sailing vessel on the lakes took the adventuring traders to Green Bay; the party then went by land. The Griffon was lost a little later, probably in a storm. La Salle went along Lake Michigan, erected Fort Miami on the site of present St. Joseph, Mich., then continued to the Illinois River. On that stream Fort Creve Coeur was built.
La Salle sent Michel Aco and Father Hennepin on an expedition to the upper Mississippi, while he himself went back to Fort Frontenac for supplies. After La Salle's departure Tonti was attacked by hostile Iroquois and was forced to flee the settlement. La Salle, returning, found the Illinois posts deserted. He set out to find Tonti and also organized (1681) a Native American federation of the Illinois, the Miami, and smaller tribes to fight the Iroquois.
He was reunited with Tonti at Mackinac Island, and the two men with Father Zenobe Membré and a small party descended the Mississippi to its mouth, arriving Apr. 9, 1682. La Salle took possession of the whole valley, calling the region Louisiana. Tonti went back to the Illinois and at Starved Rock began construction of a village; La Salle joined him, and Fort St. Louis was completed (1682-83).
La Salle was deprived of his authority by the new governor in 1683 and went to France, leaving Tonti in the Illinois country. Given power to colonize and to govern the region between Lake Michigan and the Gulf of Mexico, La Salle set out (1684) with four ships for the mouth of the Mississippi. He never reached it. With three of his ships La Salle reached the Gulf of Mexico; but because of the sandy sameness of the coastline he was unable to find the Mississippi. He and his men landed on the Texas shore, probably on Lavaca Bay. They made futile attempts to reach the Mississippi overland, and the men grew mutinous. On the third attempt the explorer was murdered by his own men.
Original narratives are translated in I. J. Cox, The Journeys of René Robert Cavelier, Sieur da la Salle (2 vol., 1922; repr. 1973). A classic account is F. Parkman's La Salle and the Discovery of the Great West (1889, repr. 1968). See biographies by R. F. Lockridge (1931) and E. B. Osler (1967).