Trikala is a city in western Thessaly, the capital of the Trikala Regional Unit and the Municipality of Trikkaion. The city is crossed by the Letheios River, which is a tributary of the Peneios River. According to the National Statistical Service's 2011 Census, Trikala had a population of 61,653 residents, while the Municipality of Trikkaion had 81,355 residents. It is located very close to the Meteora of Kalambaka and the mountainous range of southern Pindos, where well-known destinations such as Elati, Pertouli, and Pyli can be found.

The city of Trikala is built on top of the ancient city of Trikka or Trikke, which was founded around the 3rd millennium BC and was named after the nymph Trikke, the daughter of Peneios or, according to some, Asopos River. The city was an important center in antiquity, as it was the home and base of Asclepius, who is now a symbol of the Municipality of Trikkaion and was also the city's king. In the area, there was one of the most significant and ancient Asclepius temples of the time. According to Homer's "Catalogue of Ships" in the Iliad, the city is said to have participated in the Trojan War on the side of the Greeks, with thirty ships and leaders being the physician sons of Asclepius, Machaon and Podalirius. The city was the capital of a kingdom during the Mycenaean period and later became the center of the Estiaeotis region, which encompassed roughly the present-day area of the Trikala Regional Unit and is described by the geographer Strabo.

Throughout its history, the city of Trikala and the surrounding area saw various invaders in the Balkan region: Goths (396), Huns (447), Slavs (577), Bulgarians (976-1025), Normans (1081), Catalans (1309-1311), and, from 1204 onwards, the Franks. It later returned to the Byzantine Empire and the Despotate of Epirus. In the early centuries after Christ, the city and the region experienced the presence of various invaders in the Balkans: Goths (396), Huns (447), Slavs (577), Bulgarians (976-1025), Normans (1081), Catalans (1309-1311), and from 1204 onwards, the Franks. Later, the city and the region became part of the Byzantine Empire and the Despotate of Epirus. In the early 11th century, the city is mentioned with its current name, Trikala, in Anna Komnene's Alexiad. The city was finally conquered by the Ottomans in 1395 and became an important center for crafts, especially woolen textiles and leather products. It became the capital of the Sanjak of Trikala, a large region that included Thessaly and part of mainland Greece, from the beginning of Turkish rule until 1770. It also served as a significant cultural center, as the Trikala School (later known as the Greek School), which operated here for a large part of the Turkish period (1543-1854), had renowned teachers of the time, including Dionysius the Philosopher. In 1601, Metropolitan Bishop of Larissa and Trikala, Dionysius the Philosopher, proclaimed a revolt against the Turks with the motto "Trikala will regain Byzantium," but it ultimately failed.