Thessaly occupies the east side of the Pindus watershed, extending south from Macedonia to the Aegean Sea. The northern tier of Thessaly is defined by a generally southwest-northeast spur of the Pindus range that includes Mount Olympus, close to the Macedonian border. Within that broken spur of mountains are several basins and river valleys. The easternmost extremity of the spur extends southeastward from Mt. Olympus along the Aegean coast, terminating in the Magnesia Peninsula that envelops the Pagasetic Gulf (also called the Gulf of Volos), and forms an inlet of the Aegean Sea. Thessaly's major river, the Pineios, flows eastward from the central Pindus Range just south of the spur, emptying into the Thermaic Gulf.
The Trikala and Larissa lowlands form a central plain which is surrounded by a ring of mountains. It has distinct summer and winter seasons, with summer rains augmenting the fertility of the plains. This has led to Thessaly occasionally being called the "breadbasket of Greece".
The region is well delineated by topographical boundaries. The Chasia and Kamvounia mountains lie to the north, the Mt. Olympus massif to the northeast. To the west lies the Pindus mountain range, to the southeast the coastal mountains of Óssa and Pelion.
Several tributaries of the Pineios flow through the region.