From Neolithic times to the present day, significant cities flourish within the boundaries of the Municipality of Alexandroupolis, and the region develops a unique culture.

The place inhabited by the Ancient Cicones, where all common types of megalithic monuments are found (fortified acropoleis, outdoor sanctuaries for the worship of the sun and stars, anthropomorphic rock carvings), is subsequently settled by colonists from Samothrace who found Samothracian Perai, with significant cities such as Mesembria, Zone, and Sali.

The city of Sali corresponds to present-day Alexandroupolis, and in Roman times, the area served as a parking and horse-changing space. The city of ancient Doriscus was a strategic hub for the armies of Darius, Xerxes, Philip, and Alexander, connecting Asia with the rest of Greece. Doriscus is mentioned even in the early years of the Roman Empire. It is speculated that the Roman Emperor Trajan, by looting, destroyed it to create Traianopolis, the new dominant city. The organization of the road network of the Egnatian Way provides the opportunity for significant cities (Traianopolis, Vira, Makri) and monastic complexes (Panagia Kosmosotira in Feres, the cave temple of the Holy Theodores), protected by powerful military installations (Potamos or Avanta castles), to thrive during the Byzantine period. The region plays a significant role, being the immediate neighbor of Constantinople.

For reasons that have not yet been ascertained, the cities of Sali, Zone, Druis, and Serreio were destroyed at some point, leveled, and erased from the written records of descriptions. The place became an endless forest, mainly of oaks. This forest, which the locals from the surrounding areas called Dede-Agach, was managed by three Turkish feudal lords, who had thousands of acres for cultivation and pastures.

After the Russo-Turkish War, fishermen from Ainos, Makri, and Maroneia formed a small settlement - the future Alexandroupolis - which gradually grew and developed rapidly with the establishment of the railway station. The settlement began in the 1850s, and in the following decades, with the arrival of the Russians, a city plan for the coastal area, from the central boulevard to the sea, was formed.

During the Balkan Wars, Dedeagach passed from the hands of the Ottomans to the Bulgarians, but after the Treaty of Neuilly and a temporary Interallied Administration, the area was incorporated into Greece on May 14, 1920. After the Asia Minor Catastrophe and the Population Exchange, many refugees from Northern Thrace (Eastern Rumelia), Eastern Thrace, and Asia Minor sought refuge in the area. During the Second World War, Alexandroupolis remained under Bulgarian occupation for 3 years (1941-1944). The end of the war marked the beginning of the city's development economically, demographically, and culturally.

Today, Alexandroupolis is experiencing rapid economic development with the Egnatia Odos, the airport, the port, and the railway station as driving forces, and it offers a high quality of life with environmental balance and intense cultural activity. In 2011, according to the "Kallikratis" Program, the former municipalities of Alexandroupolis, Traianoupolis, and Feres were merged, creating the new Municipality of Alexandroupolis with an area of 1,217 square kilometers, with its seat in Alexandroupolis and its historical seat in Feres.