The shake-up, aimed at reinvigorating Samaras's struggling conservative-Socialist coalition, comes just weeks after its defeat in EU elections to the country's main opposition, the radical left-wing Syriza party.
Syriza beat Samaras's ruling centre-right New Democracy into second place in the May poll, gaining more than 26 per cent of the vote.
The reshuffle saw the replacement of more than a dozen ministers, including health, education, development and interior, government spokeswoman Sophia Voultepsi announced today.
Most significantly, Finance Minister Yannis Stournaras was replaced by 59-year-old economist and university professor Guikas Hardouvelis.
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Syriza made significant gains in EU elections on a campaign opposing the harsh austerity measures passed by the Greek government in return for a massive USD 330 billion bailout funded jointly by the European Union and the IMF.
Syriza's 39-year-old leader Alexis Tsipras called the vote a "referendum" on austerity.
Following Syriza's victory, speculation has been rife that Stournaras, who played a key role in the EU and IMF bailout negotiations, may be replaced.
It is thought that Stournaras will leave to head the Bank of Greece, where current governor George Provopoulos's term expires on June 21.
Elsewhere in the cabinet, positions held by Samaras's coalition partners, the socialist Pasok party, remained intact.
The party's president, Evangelos Venizelos, remains deputy prime minister and minister of foreign affairs.
Similarly, socialist Yannis Maniatis remains as environment minister and Michalis Chryssohoides retains the post of transport minister.