The ceremony came a day after his resounding win over left-wing Alexis Tsipras, who led the country through the final years of its international bailouts.
Mr Mitsotakis’ New Democracy party won 39.8 per cent of the vote, giving him 158 seats in the 300-member parliament, a comfortable governing majority.
Mr Tsipras’ Coalition of the Radical Left, or Syriza, gained 31.5 per cent.
The extremist right-wing Golden Dawn, Greece’s third largest party during the height of the financial crisis, failed to make the 3 per cent threshold to enter parliament.
Mr Mitsotakis, 51, arrived at the presidential mansion for the official swearing-in accompanied by his wife and three children, with the ceremony conducted by Archbishop of Athens Ieronymos.
Mr Mitsotakis will have to move fast to deal with the myriad of problems still plaguing the economy.
Europe’s finance ministers were meeting in Brussels yesterday to discuss Greece, which still has stringent fiscal targets to meet even though it no longer directly receives bailout loans.
“I assume the governance of the country with full awareness of the national responsibility,” Mr Mitsotakis said in his victory speech on Sunday night.
“I know of the difficulties that lie ahead for me and for my associates. But I draw strength from the strength of the people.”
Greece’s economy shrank by a quarter and poverty and unemployment levels soared during the country’s nearly decade-long financial crisis.
Although its finances are on the mend and the economy is expected to grow by 2.2 per cent this year, it still has a long way to go to make up the economic output lost.
The country’s debt stands at about 181 per cent of annual GDP and Greece has pledged to continue producing large primary surpluses - the budget excluding debt servicing - of more than 3 per cent of GDP for years to come.
Mr Mitsotakis said after his victory he would stick to his campaign pledges of lowering taxes, attracting investments and cutting through red tape to make Greece more business-friendly.
“New Democracy’s clear victory in Greece’s parliamentary elections yesterday will be welcomed by investors,” said economics consultancy Capital Economics in a research note.
“But it will not be a game changer for the economy, not least because the government will still be constrained by its membership of the single currency and its ‘surveillance’ agreement with the EU.”