The prefecture of Lassithi covers the eastern end of the island. The mountain range in this area is the Dikte. Its tallest peak is Mount Dikte, 2,148 metres above sea level. The prefecture has four provinces: Mirabelo, Lassithi, Ierapetra, and Sitia. The major cities are Agios Nikolaos, Ierapetra, and Sitia. The earliest settlements in Crete are in this prefecture, including the palaces of Zakros, Praisos, Mochlos, Vasiliki, and Gournia. An important early Greek city, Lato, is near Kritsa. The fine Archaeological Museums of Agios Nikolaos and Sitia display some of the artefacts from these and other excavations.

According to legend, the Dikteon Andron Cave, on the Lassithi Plateau, was the birthplace of Zeus. The area around Agios Nikolaos is not only the most developed area for tourism but one of the most interesting. The church of the Panagia Kera near Kritsa contains some of the best-preserved Byzantine frescoes in Crete. Elounda has one of the strongest Venetian forts built on Crete. The area of Sitia is full of Byzantine churches and Venetian villas, as well as ancient Minoan sites. The famous Toplou Monastery has a museum displaying its well-known icon collection. The area also has very good beaches with many coves between Ierapetra and the Kapsa Monastery that offer excellent swimming. The area of Vai has a unique palm grove that attracts many people.

Ierapetra is one of the four provinces of Lassithi. Its capital is the city of Ierapetra. The province of Ierapetra has many good examples of Byzantine churches with frescoes in them There are two monasteries of note, Exakousti Monastery and Faneromeni Monastery. East of Ierapetra there are many fine beaches in the Makrigialos Bay.

Sitia is the largest province of Lassithi in area and population. Its capital is the city of Sitia. The mountains are lower then in other parts of the island, but have a distinctive and varied landscape. The earliest Minoan settlements are here at Mochlos, Palaikastro, and the Minoan palace of Zakros. The Kilada ton Nekron (Valley of the Dead) in Zakros and the Hellenistic site of Itanos near Vai are also of interest. There are many Byzantine churches in the area. Evidence of the Venetian era may be seen in the villages of Etia and Handras. The monastery of secluded Kapsa offers visitors a view of monastic life; there is much to see and do in this province.