Archaeological excavations at Nosy Mangabe and Mananara Avaratra show that human habitation in Ambatosoa dates to the eighth century. In 1503,
Diogo Fernandes Pereira became the first European known to have visited Antongil Bay. Antongil Bay and Nosy Mangabe in particular served as a resupply point for Dutch, English and French ships throughout the 16th to 18th centuries. Towards the end of that period, it also became a slave-trading port. The
Tsimihety people originated in the 16th and 17th centuries in the Rantabe and Mananara valleys on the coast of Antongil Bay, but moved inland by the mid-18th century. Their departure coincides with the unification of the
Betsimisaraka nation under
Ratsimilaho, who controlled the coast from Maroantsetra south to
Toamasina. Originally fishermen, the Betsimisaraka were victims of
Mascarene (European),
Sakalava and
Sihanaka slave trafficking in the 17th and 18th centuries, but later became formidable pirates themselves, pillaging as far as the
Comoros and the East African coast in the late 18th century. The presence of small numbers of
Makoa people in the region is probably a result of these expeditions. In the last quarter of the 19th century through the beginning of the 20th century, the Tsimihety started returning to the area, settling especially around the trail connecting
Mandritsara and Mananara Avaratra, and between the Mananara and Antainambalana rivers. It was recreated on 29 June 2023 by separating the districts of
Mananara Avaratra and
Maroantsetra from Analanjirofo. The region was officially inaugurated on 26 July 2025 with the installation of Rabefenara Louis Velombity as the region's first prefect. ==Administrative divisions==