Before the arrival of the Europeans, the areas now known as Guaymas was dominated by the Guaymas, Seri and Yaqui tribes. In 1539, two Spanish ships, the Santa Agueda and El Trinidad, arrived to Guaymas Bay. They were commanded by Francisco de Ulloa, who called the area “the port of ports.”
Some small Jesuit missions in the area were founded in the 1610s and 1620s, when Jesuits founded eight mission villages with the Yaqui. The Seri strongly opposed the settlement of Europeans and resisted fiercely until 1769.
Juan María de Salvatierra and Eusebio Kino asked for permission to evangelize the area, which was received in 1697. In 1701, Salvatierra came to this area and established the Loreto mission somewhat inland from where Guaymas is now. To receive supplies by ship and evangelize the Guaymas Indians, the Jesuits founded another small mission on the bay, which they called San José de Guaymas. It was headed by Manuel Diaz. The Seri repeatedly attacked the San José mission, forcing it to be abandoned and rebuilt several times. The last time this mission was abandoned was in 1759.
In 1767, Viceroy Marqués de Croix ordered a major military offensive, the Sonora Expedition, to subdue the Seri and Pima tribes. After doing so, the Spanish colonials built an adobe fort with four towers in Guaymas, initially under the command of Captain Lorenzo Cancio. No traces of the fort remain today, but the San José mission is marked by a church located on the road leading to Empalme. Around the same time, the colonists formally mapped the Guaymas Bay and officially founded the city of Guaymas in 1769 by José Gálvez in Real de Alamos on behalf of the viceregal government. Despite the decree, no colonists settled there until the early 19th century.
In the late 18th and early 19th century, there was supposedly only one inhabitant in Guaymas, called “Tio Pepe” (Uncle Pepe), who was said to be a drunk and a thief. At the beginning of the 19th
