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The department originated in the old Ministry of Northern Greece, which was renamed the Ministry of Macedonia and Thrace on 19 August 1988.
The ministry was abolished on 7 October 2009 and downgraded to a general secretariat within the Ministry of the Interior, but was re-established on 21 June 2012. On 27 January 2015, it was again demoted to a sub-ministry within the Ministry of the Interior.