The French colonization of Texas began with the establishment of a fort in present-day southeastern Texas. It was established in 1685 near Arenosa Creek and Matagorda Bay by explorer Robert Cavelier de La Salle. He intended to found the colony at the mouth of the Mississippi River, but inaccurate maps and navigational errors caused his ships to anchor instead 400 miles (640 km) to the west, off the coast of Texas. The colony survived until 1688. The present-day town of Inez is near the fort's site. The colony faced numerous difficulties during its brief existence, including Native American raids, epidemics, and harsh conditions. From that base, La Salle led several expeditions to find the Mississippi River. These did not succeed, but La Salle did explore much of the Rio Grande and parts of east Texas.

During one of his absences in 1686, the colony's last ship was wrecked, leaving the colonists unable to obtain resources from the French colonies of the Caribbean. As conditions deteriorated, La Salle realized the colony could survive only with help from the French settlements in Illinois Country to the north, along the Mississippi and Illinois Rivers. His last expedition ended along the Brazos River in early 1687, when La Salle and five of his men were murdered during a mutiny. Although a handful of men reached Illinois Country, help never made it to the fort. Most of the remaining members of the colony were killed during a Karankawa raid in late 1688, though four children survived after being adopted as captives. Although the colony lasted only three years, it established France's claim to possession of the region that is now Texas. The United States later claimed, unsuccessfully, this region as part of the Louisiana Purchase because of the early French colony.

Spain learned of La Salle's mission in 1686. Concerned that the French colony could threaten Spain's control over the Viceroyalty of New Spain and the unsettled southeastern region of North America, the Crown funded multiple expeditions to locate and eliminate the settlement. The unsuccessful expeditions helped Spain to better understand the geography of the Gulf Coast region. When the Spanish finally discovered the remains of the French colony at the fort in 1689, they buried the cannons and burned the buildings. Years later, Spanish authorities built a presidio at the same location. When the presidio was abandoned, the site of the French settlement was lost to history. The fort was rediscovered by historians and excavated in 1996, and the area is now an archaeological site. In 1995, researchers located the ship La Belle in Matagorda Bay, with several sections of the hull remaining virtually intact. They constructed a cofferdam, the first to be used in North America to excavate the ship as if in dry conditions.

René-Robert Cavelier, Sieur de La Salle (; November 22, 1643 – March 19, 1687), was a 17th-century French explorer and fur trader in North America. He explored the Great Lakes region of the United States and Canada, the Mississippi River, and the Gulf of Mexico. He is best known for an early 1682 expedition in which he canoed the lower Mississippi River from the mouth of the Illinois River to the Gulf of Mexico; there, on 9 April 1682, he claimed the Mississippi River basin for France after giving it the name La Louisiane. One source states that "he acquired for France the most fertile half of the North American continent".La Salle is often credited with being the first European to traverse the Ohio River, and sometimes the Mississippi as well. It has now been established that Joliet and Marquette preceded him on the Mississippi in their journey of 1673–74, and the existing historical evidence does not indicate that La Salle ever reached the Ohio/Allegheny Valley.