According to mythology the city was built by King Agrion. Agrinio is the largest city of Aitoloakarnania. It was temporarily renamed to Vrachori during the Turkish domination. After the liberation from the Turks and its integration into the free Greek state in 1832, it once again reclaimed its ancient name, Agrinion. The ancient city was located in the neighboring Zapaditi (today’s Megali Hora), but in recent years many ancient ruins have been found even in the center of the present city.
Agrinio experienced rapid growth in the early 20th century, when it turned to tobacco cultivation. The Papastratos, Panagopoulos and Papapetros families built huge warehouses and tobacco processing plants. The town received Greek refugees after the Asia Minor catastrophe and was always a destination for domestic immigration from the mountains of the prefecture, Evritania and Epirus.