Ka cika wannan jumla: Sanin Slav a yankin ya sa aka zaɓi 'yan'uwa biyu daga Tasalonika, Saints Cyril da Methodius, don su juyar da Slavs zuwa Kiristanci. Bayan kamfen na Basil II, duk Makidoniya ta koma jihar Byzantine. Bayan yaƙin Crusade na huɗu na 1203<unk>1204, an kafa daular Crusader na ɗan gajeren lokaci, Masarautar Thessalonica, a yankin. Wanda ya kirkiro Despotate na Girka na Epirus, Theodore Komnenos Doukas a 1224, lokacin da Macedonia ta Girka da birnin Thessaloniki suke a zuciyar daular Thessaloniki mai gajeren lokaci. Komawa zuwa Daular Byzantine da aka maido ba da daɗewa ba, Girka Macedonia ta kasance a hannun Byzantine har zuwa 1340s, lokacin da Sarkin Serbia Stefan Dušan ya ci duk Makidoniya (ban da Thessaloniki, da kuma Veria). Bayan da
Yaƙin Maritsa (1371), an sake kafa mulkin Byzantine a yankuna na gabas, gami da Serres. A lokacin 1380s, yankin ya ci gaba da cin nasara a hankali ta hanyar Ottomans, tare da Serres yana riƙe har zuwa 1383, da Thessaloniki har zuwa 1387. Bayan ɗan taƙaitaccen tazarar Byzantine a cikin 1403<unk>1430 (a cikin shekaru bakwai da suka gabata wanda aka ba da birnin ga Venetians), Thessaloniki da kewayenta sun koma ga Ottomans.