Manuel Gayoso de Lemos Amorín y Magallanes was born in Oporto, Portugal, on May 30, 1747, the son of Spanish consul Manuel Luis Gayoso de Lemos y Sarmiento and Theresa Angélica de Amorín y Magallanes. He was educated in England and joined the Spanish Lisbon Regiment as a cadet on July 7, 1771. He was commissioned sublieutenant on July 20, 1772, and was promoted through the years, reaching the rank of brigadier on September 4, 1795.
On November 3, 1787, he was named governor of the fort and district of Natchez. He served at that post from 1789 until August 1797, during which time he encouraged American settlers, established posts as far north as Missouri, and organized militia, naval units, and defenses of the frontier to guard against possible attacks from Indians, American frontiersmen, or Jacobins. His valuable services in persuading the southern Indians to sign treaties in 1792, 1793, and 1795 secured a buffer zone between the American settlements and Spanish Louisiana. His close contacts with Gen. James Wilkinson during the so-called "Spanish Conspiracy" introduced him to Philip Nolan, with whom he was tempted to form a business partnership in 1797 involving the importation of Texas horses into Louisiana and the trading of goods with Texas and Mexico.
Gayoso was appointed governor general of Louisiana and West Florida on October 28, 1796. He took office on August 5, 1797, and died in New Orleans of yellow fever on July 18, 1799, as Americans moved into the Natchez District. He was married three times: to Theresa Margarita Hopman y Pereira of Lisbon, to whom two children were born; to Elizabeth Watts of Philadelphia; and to Margaret Cyrilla Watts of Louisiana, to whom one son was born. Gayoso's correspondence with governors of Texas and the viceroy of New Spain during 1797–99 concerned the activities of Philip Nolan, whom Gayoso considered a dangerous enemy of Spain, and the preservation of Louisiana as a barrier to American expansion into Texas and New Spain.