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Early Modern Period

Eritrea's pre-colonial period had four distinct regions that were divided by geography, thus, having limited contact with each other. The regions were ruled as follows: the Abyssinian (Tigrinya-speaking Christians) in the highlands, the nomadic Tigre and Beni Amer clans of the western lowlands, the Arabic Muslims of Massawa and Dahlak, and the pastoralist Afars found in the Dankalia.

After the decline of Aksum, the Eritrean highlands fell under the domain of the Christian Zagwe dynasty, and later, fell under the sphere of influence of the Ethiopian Empire. The area was at first known as Ma'ikele Bahri ("between the seas/rivers", i.e. the land between the Red Sea and the Mereb river). The entire coastal domain of Ma'ikele Bahri was under the Adal Sultanate during the reign of Sultan Badlay ibn Sa'ad ad-Din. The state was later reconquered by the Ethiopian Emperor Zara Yaqob and renamed the Medri Bahri ("Sea land" in Tigrinya, although it included some areas such as Shire in Ethiopia on the other side of the Mereb, today in Ethiopia). With its capital at Debarwa, the state's main provinces were Hamasien, Serae, and Akele Guzai.

The first Westerner to document a visit to Eritrea was the Portuguese explorer Francisco Alvares in 1520. His books have the first description of the local powers of Tigray, the kingdom of Axum and Barnagais (the lord of the lands by the sea)

The contemporary coast of Eritrea was the one that guaranteed the connection to the region of Tigray where the Portuguese had a small colony, and therefore the connection to the interior Ethiopian, allies of the Portuguese. Massawa was also the stage for the 1541 landing of troops by Cristóvão da Gama in the military campaign that would eventually defeat the Adal Sultanate in the final battle of Wayna Daga in 1543.

By 1557, the Ottomans had succeeded in occupying all of northeastern present-day Eritrea for the next two decades, an area which stretched from Massawa to Swakin in Sudan. The territory became an Ottoman governorate, known as the Habesh Eyalet. Massawa served as the new province's first capital. When the city became of secondary economical importance, the administrative capital was soon moved across the Red Sea to Jeddah. The Turks tried to occupy the highland parts of Eritrea in 1559 and withdrew after they encountered resistance. They were pushed back by the Bahri Negash and highland forces. In 1578 they tried to expand into the highlands with the help of Bahri Negash Yisehaq, who had switched alliances due to a power struggle. Ethiopian Emperor Sarsa Dengel made a punitive expedition against the Turks in 1588 in response to their raids in the northern provinces, and apparently by 1589, they were once again compelled to withdraw their forces to the coast. The Ottomans were eventually driven out in the last quarter of the sixteenth century. However, they retained control over the seaboard until the establishment of Italian Eritrea in the late 1800s.

In 1734, the Afar leader Kedafu, established the Mudaito Dynasty in Ethiopia, which later also came to include the southern Denkel lowlands of Eritrea, thus incorporating the southern Denkel lowlands to the Sultanate of Aussa.