The area was originally inhabited by Muskogean language peoples. The Pensacola people lived there at the time of European contact, and Creek people frequently visited and traded from present-day southern Alabama. Spanish explorer Tristán de Luna founded a short-lived settlement in 1559. In 1698 the Spanish established a presidio in the area, from which the modern city gradually developed. The area changed hands several times as European powers competed in North America. During Florida's British rule (1763–1781), fortifications were strengthened.
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Public primary and secondary education schools in Pensacola are administered by the Escambia County School District. The current superintendent of schools for Escambia County is Malcolm Thomas. The University of West Florida, located north of the city, is the largest post-secondary institution in the area. It also has the largest library in the region, the John C. Pace Library.
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Pensacola is home to a small (0.2% of city residents) but significant Jewish community, whose roots date mostly to German Jewish immigrants of the mid-to-late 19th century. There were also Sephardic Jewish migrants from other areas of the South, and immigrants from other areas of Europe. The first Florida chapter of B'nai Brith was founded downtown in 1874, as well as the first temple, Beth-El, in 1876. Apart from the Reform Beth-El, Pensacola is also served by the Conservative B'nai Israel Synagogue. Paula Ackerman, the first woman who performed rabbinical functions in the United States, was a Pensacola native and led services at Beth-El.
In 1559, Tristán de Luna y Arellano landed with some 1,500 people on 11 ships from Veracruz, Mexico. The expedition was to establish an outpost, ultimately called Santa María de Ochuse by Luna, as a base for Spanish efforts to colonize Santa Elena (present-day Parris Island, South Carolina.) But the colony was decimated by a hurricane on September 19, 1559, which killed an unknown number of sailors and colonists, sank six ships, grounded a seventh, and ruined supplies.