Evidence of human inhabitance in the area reaches back to Neolithic age. The city's history begins in the second half of the 7th century BC when Parian settlers, who in the meantime had colonized the island of Thassos, passed on the opposite mainland coast and founded a new colony called Neapolis. Around the same time, another walled settlement was created in the area of Kipoupoli, named Antisara.
During Macedonian rule Kavala, as a harbor serving Filippi, gained great prosperity, after Philip II -father of Alexander the Great -annexed it.
During the Roman Empire the city upgraded into a major port in the region and a travel station, as in front of its walls was passing through Via Egnatia (the main thoroughfare of the Roman Empire connecting Durres to Istanbul).
In 45A.D. the Apostle Paul visited Kavala on his way to Philippi, where he founded the first Christian community in Europe. In the eighth century the city was known as Christoupolis. After intense adventures and struggles, during the times of the Crusades was conquered and completely destroyed by the Turks (about 1391). After almost a century of desolation, and in the second half of the 15th century the city appears again under the current name and quickly developed into a major port. In 1864 the Greek people got permission from the Turkish state and created the first neighbourhood outside the walls in the area of St. John