In 12,058 G.E. the population of Santanni attempted to rebel against the Galactic Empire. Raych Seldon, son of psychohistorian Hari Seldon, was killed in the rebellion, valiantly defending the University of Santanni.
After the founding of the Foundation, Santanni traded with it until the trade route was cut off by the rebellion of Anacreon. One known thing of Santanni make was the cigar box possessed by Jord Fara, and later by Salvor Hardin.
It was captured in the early stages of the war with Kalgan. After the death of the Mule, Santanni was instrumental in breaking the siege on Terminus levied by the Mule's successor, Han Pritcher in 308 F.E.