Exploring North America: La Salle traveled from France to Quebec, New France (Canada), in late 1667. He was determined to find a water passage to the east through North America. Leaving Montreal in July, 1669, La Salle crossed Lake Ontario, Lake Erie, and other places which are not documented (he did not return to Montreal until late 1670, and may have traveled down the Ohio or Mississippi River). La Salle made many exploring trips during the years 1671 to 1673.

La Salle returned to France in 1677, getting permission form the King to explore the area between Florida, Mexico and New France (Canada). He returned to Canada in 1678 with his friend, Henri de Tonty, and others.

In Canada, they constructed a fort on the Niagara River (between Ontario and New York) and built a ship called the Griffon, which they used to explore the Great Lakes. They sailed on August 7, 1679, traveling across Lake Erie and Lake Huron. They traveled across land to Lake Michigan, which they paddled across in canoes. Returning, they discovered that the Griffon was lost, the fort at Niagara had burned down, and many men had deserted their posts, robbing supply stores.

Traveling the Length of the Mississippi River: On a 1681 expedition, La Salle and about 40 men again headed to the Mississippi River. They reached the Mississippi River on February 6, 1682, then headed down it in canoes. They built Fort Prud'homme at what is now Memphis, Tennessee, and later reached the Gulf of Mexico on April 9, 1682, where they built a cross. They claimed all the land along the Mississippi River for France. Their return to New France was beset by illness and Indian attacks.

Settling Gone Awry: La Salle returned to France in 1683, but sailed to the New World again in 1684 with four ships, intending to start a colony in the Mississippi River Valley (the king actually wanted him to travel to the Rio Grande to take over Spanish mines, but La Salle lied and told him that the Mississippi was farther north than it is). The expedition lost a vital supply ship en route, and mistakenly landed in Matagorda Bay, near what is now Houston, Texas, where one ship ran aground. La Salle's men shot Indians who took supplies from the wrecked ship, making enemies of the local Indians. One ship returned to France with a disgruntled crew.

Stranded in Texas: The French expedition built a fort at the mouth of the Lavaca River, and explored the area. The last remaining ship was wrecked by a drunken pilot in April 1686, stranding the French in Texas. The 20 men traveled up the Lavaca River, trying to locate the Mississippi River so they could follow it north into the French missions in the Great Lakes region. Most of the men in this expedition died, and the 8 survivors returned to the fort in October, 1686. On a second try, La Salle and 17 others set out (25 people remained at the fort); in a few months, a group of five mutineers shot and killed La Salle (near Navasota, Texas) on March 19, 1687. They left his body for the animals to eat. The rest of the expedition made it to Montreal in 1688, but those at the fort were killed by the Karankawa Indians.