The Achelous rises at about 2,000 metres on the eastern side of Mount Lakmos, in the Pindus range, and flows south for about 220 km to the Ionian Sea. Its upper course is known locally as Aspropotamos, which means "the white river". There it forms the border between Epirus and Thessaly. Further south, the river forms borders between five regional units: Trikala, Karditsa, Arta, Evrytania and Aitoloakarnania.

Its tributaries include the Agrafiotis and the Tavropos (Megdovas), which meet it in Lake Kremasta. Dams at Mesochora (2001), Kremasta (1965), Kastraki (1969) and Stratos (1989) control its flow, and the three lower dams hold large reservoirs. Lake Kremasta, the largest of them, covers about 80 square kilometres. Below Stratos, the river crosses the plain of Aitoloakarnania and reaches the sea about 29 km west of Messolonghi, through a delta of marshes and river forest.

Rafting trips run on two sections of the upper river. The first starts at the Alexiou bridge and ends just before the Mesochora dam. It has grade II and III rapids, clear blue water and white pebble beaches for stops, and the valley widens as you go, with views of the peaks of the Pindus. The second starts below the Mesochora dam and runs for about 15 km to the village of Terpna, past the forests of the Tzoumerka mountains. Its rapids, of grade II and III, suit beginners.

Further south, Lake Kremasta, the large reservoir in Evrytania, is used for canoeing and kayaking, with organised trips, and for boat rides. The lake spreads into long, narrow arms between the mountains, and a boat needs six to seven hours to travel all of it. Two long road bridges cross the lake, at Tatarna and at Episkopi.

Near its springs, the river passes the villages of the Aspropotamos area, at more than 1,000 metres among fir forests and the peaks of the Pindus. Chaliki, 25 km from the mountain town of Metsovo, has three stone bridges over the streams that feed the river. The village of Kalliroi lies about 20 km further down the valley.

Further south, where the river forms the border between Karditsa and Arta, the valley has narrow gorges, water mills and old stone bridges, such as those of Avlaki and Templa. It also has perataries, cable crossings built in the 1950s so that villagers could cross the river. In summer, the river leaves small beaches along its banks, where people swim in blue-green water.

The river ends in a wide delta on the Ionian coast, west of Messolonghi. Its lower course and mouth are part of a national park that also covers the lagoons of Messolonghi and Aitoliko and the mouth of the Evinos. Great white egrets and flamingos feed in these wetlands. Off the mouth, the Echinades, a group of small islands, have a large colony of shags, a kind of sea cormorant.

Near the village of Lesini, the Fraxos forest, a forest of ash trees, has been protected as a natural monument since 1985. At Srofa, on the coast, loggerhead sea turtles lay their eggs on the beach. Much of the farmland around the delta is planted with orange groves.

On a low hill near the mouth stand the walls, theatre and shipsheds of ancient Oiniades. In ancient times the hill rose above marshes of the Achelous, which protected the city. Its shipsheds, cut into the rock, are known for how well they have survived. The theatre looks out over the river and the plain, and it hosts a yearly festival.

In myth, the river was a god, Achelous. He fought Heracles for the right to marry Deianira, taking the shape of a bull, and Heracles broke off one of his horns. In the version of the Roman poet Ovid, nymphs filled the horn with fruit and flowers, and it became the horn of plenty.