The Espiritu Santo was part of Antonio Corzo’s flotilla, which sailed from Veracruz to Spain with 4 ships: San Esteban, San Andrés, Espíritu Santo and Santa María de Yciar.
Three of them were wrecked in a storm on April 29, including the Espiritu Santo. Many of the 300 sailors and passengers drowned while trying to reach shore; about thirty took a boat to seek help; almost all the rest died of thirst or starvation, or were killed by Karankawa Indians. The Spaniards sent a salvage expedition under the command of Ángel de Villafañe, who protected the site from looters coming from the settlements of Tampico and Pánuco, until the main salvage crew arrived. They were led by García de Escalante Alvarado, who had bought six ships to recover coins belonging to Emperor Charles V, ingots, and the rest of the cargo.
The remains were located in 1964. The Espiritu Santo was located by a female diver in 1964, who removed objects from the wreck until she reported the find. In 1967, the treasure hunter company Platoro, Ltd., extracted about 500 objects from the wreck, including a gold ingot, jewelry and navigational instruments. The Texas State Antiquities Act of 1969 protected the wreck and prevented treasure hunters from working there.
Since 1974, the wreck of the Espíritu Santo has been part of the Mansfield Cut Underwater Archaeological District.