Christopher Columbus made landfall on the nearby Paria Peninsula in Aug 1498. Two years later, a settlement had been established at Santiago de Cubagua (later called Nueva Cádiz) to exploit the pearls which grew in its waters. Cubagua became a centre for pearling and for slavery, as the local Indians were used, under appalling duress, to dive into the oyster beds.
By 1541, when Santiago was destroyed by an earthquake and tidal wave, the pearl beds had been almost exhausted, but the Greek word for pearl, margarita, was retained for the main island of the group.
Margarita, and the nearest town on the mainland, Cumaná, were strongholds of the forces for the independence of South America from Spain. Between 1810 and 1817, the island was the scene of revolts and harsh Spanish reprisals. The liberator Simón Bolívar declared the Third Republic, and was himself declared Commander in Chief of the Liberating Army, at Villa del Norte (now Santa Ana) in 1816. After the war, the name of Nueva Esparta (maintaining the Greek allusion) was conferred in recognition of the bravery of Margarita in the struggle. Subsequent events have been nothing like so heroic, with life revolving around fishing and small agriculture. After a regeneration of the the pearl industry at the end of the 19th century, it has gone into decline, the oyster beds having all but disappeared through disease.