[9] Kotzias broke with the Communist Party after the majority's decision to co-ally with the conservatives in order to bring Prime Minister Andreas Papandreou to trial for corruption.

Since January 2015 Kotzias is Foreign Minister in a cabinet in coalition with Independent Greeks, a right wing conservative party that also opposes austerity.

He supports the view that even a relatively small state, in terms of economic power, can take advantage of the changes that occur in a global context and increase its capacities to allow it to exercise an autonomous foreign policy according to the national interest.

Supporting the view that the world has already begun to move towards multipolarity, Kotzias believes that states that wish to increase their influence and capacities should seek to forge concrete relations with the emerging powers (BRICS).

In one of his latest books "The Colony of Debt", Nikos Kotzias claims that the European Union is developing empire characteristics, as it perceives markets, the bureaucracy in Brussels and Germany as focal elements of its structure.

"[15] In the same night of Kotzias's appointment, the Greek Ministry of Foreign Affairs released a statement, issuing Greece's unwillingness to agree to key passage of statement, delaying agreement for further EU sanctions against Russia-backed separatists in Ukraine, before the extraordinary meeting of the EU Council of Foreign Ministers, which was scheduled on 29 January 2015 in Brussels.

"[16] The 29 January meeting resulted to an improved and softened version of the statement, extending the ongoing sanctions but avoiding to include further measures, mainly due to the position that the Greek minister held.

On 17 October 2018 Kotzias submitted his resignation, a day after a cabinet meeting during which he clashed over the Prespa agreement with Defense Minister Panos Kammenos, who has opposed the deal.