The island was once used by an Arab slave trader to contain the more troublesome slaves he had brought from the African mainland to prevent their escape before shipping them to the Arabian purchasers. Many slaves were also dumped on the island and auctioned at the Zanzibar slave market.

In 1893, Lloyd Mathews built the prison. The prison idea was to send violent criminals from the Tanganyika Mainland to the Prison Island. Instead, Prison Island ended up being used as a quarantine center for the yellow fever epidemic that once raged through the region. The Island remained in the ownership of the government, who converted the newer quarantine buildings into a guesthouse. The old prison still remains standing, providing shelter for some of the giant tortoises which can now only be found on this island.