There were settlements dating back to the Neolithic period where Heraklion stands today. It is believed to have been the site of the Minoan harbour of Knossos, although very little evidence has been found to confirm this.

The Saracens took possession of the town in 824 AD and was renamed El Khandak, Moat Fort, when they built the large moat around the town. The town was recaptured by the Byzantium Emperor in 961 after many fruitless attempts. After a period of rule that spanned 2 centuries this empire was dissolved by the Crusaders, who took over the rule of Crete. It was relinquished to the Venetians for 1,000 silver coins. Candia, as the Venetians named it, flourished under their rule as a centre of the arts. Many craftsmen and artists found sanctuary here after the fall of Constantinople in 1453.

The Venetians commenced the building of the fort in 1462 and it took them over 100 years to complete. The walls covered 4 km and were built in triangular style with seven bastions. They also built the harbour as well as other eminent buildings. The strategic significance was shown when it lay under siege by the Ottoman Empire for 21 years. The town surrendered in 1669 after 30,000 Venetians and 100,000 Turks had lost their lives.

The Ottoman occupation was offensive to the Cretans as they were forced to convert to Islam. From 1820 onwards there was the resistance fight against the Turks until their departure. Crete was annexed to Greece in 1913.

Due to the strategic position, it was again the focus of the Germans during WWII with bombings during the Battle of Crete in 1941. The Germans stayed until 1945. After the war the city was rebuilt.