El Seibo was founded in 1502 by Juan de Esquivel, a notable a Spanish conquistadir.

The name of Santa Cruz de El Seibo, is taken from the Spanish custom of placing the Cross of Christ at the cardinal points, as protection against evils.

A cross called Asomante is still preserved, in the West Sector of the city of El Seibo.

By 1504, the Spaniards Juan Briceño and Francisco Almenara appear as residents of the area, paying the fifth to the Real Caja del Rey.

This battle took place in what is today kilometer 3.5 of the El Seibo-Hato Mayor highway, on November 7, 1808, the troops of Napoleon Bonaparte, French Emperor, and an army of Creoles under the command of General Juan Sánchez Ramírez.