It borders the regional units of Kozani to the northwest, Pieria to the northeast, the Aegean Sea to the east, Magnesia to the southeast, Phthiotis to the south, Karditsa to the southwest and Trikala to the west.

The tallest mountain in Greece, Mount Olympus (2,917 m) is situated in the northeastern part of the regional unit.

The northern part is covered with forests, but most of the regional unit is fertile land, the Thessalian Plain.

The area was invaded and was ruled by the Kingdom of Macedonia a few centuries later, and was conquered by the Roman Republic after the Third Macedonian War.

It was awarded to Greece in the Congress of Berlin in 1878, and finally incorporated into the Hellenic Kingdom in 1881, albeit parts of the modern Larissa prefecture, including Tyrnavos, Elassona and Sarantaporo, remained Ottoman.

During the Greco-Turkish War of 1897, the area was successfully invaded by the Ottomans, but in the end Greece conceded only minor territorial losses.

The Thessalian Plain is famous for its crops including fruits (watermelon and melon), vegetables (tomatoes, potatoes, cucumbers, onions, etc.

The region is directly linked to the rest of Europe through International Airport of Central Greece located in Nea Anchialos in a small distance from Larisa (26 kilometers).