[citation needed] It is part of the Kea-Kythnos regional unit and in the municipality of Kea.

The Kea Channel between Makronisos and neighbouring Kea was the site of the sinking, in 1916, of HMHS Britannic, sister ship of the RMS Titanic.After the Burning of Smyrna in 1922 and the population exchange between Greece and Turkey, Greek refugees from the Ottoman Empire were transferred to Makronisos, where a quarantine station (to minimize the spread of smallpox and typhus infection) was established.

[8] Makronisos was used as a military prison island and concentration camp from the time of the Greek Civil War until the restoration of democracy, following the collapse of the Regime of the Colonels in 1974.

Because of its history, it is considered a monument of the civil war era; therefore the island and the original structures on it are protected from alteration.

Among the prisoners of Makronisos were Apostolos Santas, Nikos Koundouros, Mikis Theodorakis, Leonidas Kyrkos and Thanasis Vengos.