When Acre fell in 1291, Henry II, last crowned King of Jerusalem, escaped to Cyprus with most of his nobles. Henry continued to rule as King of Cyprus, and continued to claim the kingdom of Jerusalem as well, often planning to recover the former territory on the mainland. He attempted a coordinated military operation in 1299/1300 with Ghazan, the Mongol Ilkhan of Persia, when Ghazan invaded Mameluk territory in 1299; he tried to stop Genoese ships from trading with the Mamluks, hoping to weaken them economically; and he twice wrote to Pope Clement V asking for a new crusade.

His reign in Cyprus was prosperous and wealthy, and he was very much involved with the justice and administration of the kingdom. However, Cyprus was in no position to fulfill his true ambition, the recovery of the Holy Land. The kingdom eventually came to be dominated more and more in the 14th century by the Genoese merchants. Cyprus therefore sided with the Avignon Papacy in the Great Schism, in the hope that the French would be able to drive out the Italians. The Mamluks then made the kingdom a tributary state in 1426; the remaining monarchs gradually lost almost all independence, until 1489 when the last queen, Catherine Cornaro, was forced to sell the island to the Republic of Venice.