Hernando de Soto is credited with naming the Mississippi River "Rio del Espiritu Santo" in 1541.

De Soto, a Spanish explorer, was one of the first Europeans to encounter the Mississippi River during his expedition through the southeastern United States. When he reached the river, he named it "Rio del Espiritu Santo," meaning "River of the Holy Spirit," in honor of the day his expedition reached the river, which coincided with the Feast of the Holy Spirit. This naming occurred long before the river was known by its current name.