According to the legend, Acqui was founded by the Greeks with the name of Caristo, then it was conquered by the Romans in 172 BC. Ancient historians like Pliny, Strabo, Seneca, Tacitus already spoke of its thermal waters, called "Aquae Statieellae".
After the fall of the Roman empire in 476 AD it became a Dukedom under the Longobards. In the 11th century it was a member of the Lombard League against Frederick Barbarossa. In 1278 it was under the Marquis of Monferrato, in 1533 it came under the power of the Gonzaga from Mantua and finally came under the power of the the Savoy.