The Prefecture of Trikala is one of the four prefectures of Thessaly and the Northwest region of Thessaly. Western borders with the prefectures of Arta and Ioannina, North to Grevena Prefecture, east with the prefecture of Larissa and South with Karditsa prefecture.

Findings in the cave Theopetra confirm the human presence in the Prefecture of the middle Paleolithic period. In the Prefecture found settlements of the Early Neolithic era, Mycenaean tombs and geometric graves.

The city with the present name Trikala, Prefecture capital, is first mentioned in the 12th century in "Alexiada" of Anna Comninis. Probably founded in the Middle Ages in the place of the very ancient Trikke or Trikis, which took part in the Trojan War along with the other cities of Greece.

In the antiquity, she was built in the left bank of the river Lithaios, it brought the name Doris and was capital of Thessalian Istiotidas. It owes her rename in Trikki  in the girl of Aesop and wife of Ypseos. King of Trikki was the Famous doctor Asklipios that is considered child of the city. The modern city of Trikala is probably built on the remains of ancient Trikki.

The city of Trikala follows the history of Thessaly, occupied by Philip II’ of Macedon, Julius Caesar, suffered big destructions from their Slavic people, Saracens and Bulgarian and afterwards the conquering of Istanbul from the Crusaders became province of despotate of Epirus. In 1993 devolved to the Turkish balance and with Sultanate Firman in 1786 the administration of Trikala were assigned in Ali Pasha of Epirus. The region has also particular interest because of her Byzantine monuments.

The 11th century monks resorted to the rocks of Meteoron, which were increased at the Ottoman domination creating a state with more from twenty monasteries. In the prefecture was developed particularly the cottage industry, from the dues of the 17^th until the beginning of 19^th century. Trikala was liberated initially by the Turkish in 1881, but after  the  war of 1897 it devolved again under their sovereignty until 1898, when it was finally liberated. The region of Trikala was challenged during World war II in October 1943,when the conquerors burned a lot of villages.