The irredentism of the Megali Idea, which had remained a strong force in Greek society since independence, gained new momentum from the liberation of territory surrounding Greece and from changes in Great Power policy in the second half of the nineteenth century. The results were conflict with the Ottoman Empire in Crete and with the Slavs in Macedonia, along with territorial gains in Thessaly and Arta.

In 1866 the first of three revolutions began on the strategically crucial island of Crete. Omission of Crete in the formation of the kingdom of Greece remained a sore point, and the island's status became more problematic as the fate of the Ottoman Empire assumed a greater role in Great Power relations. Although all the powers wished to prevent occupation of Crete by a rival, European solutions to Mediterranean crises repeatedly left Crete to the sultan, merely pressuring him to improve conditions for the Orthodox population of the island.

In the 1860s, however, the Great Powers agreed to the unification of Italy and the transfer by Britain of the Ionian Islands to Greece. As the Orthodox population and nationalist sentiments grew on Crete and King George openly supported the Cretan reunification factions, these changes also reinforced Greek advocacy of claims to Crete. The result was a guerrilla rebellion on Crete that received wide support from the Greek government and people.

Although the Cretan rebels found considerable public sympathy in the West, efforts by Russia and Serbia to profit from the Ottoman Empire's distraction in Crete brought diplomatic pressure from Britain and France. By 1869 Serbian and Russian support of the rebellion had softened, and the Ottoman fleet had used a blockade of Crete to its advantage. At the Paris peace talks of 1869, Greece agreed that Crete would remain part of the Ottoman Empire, with the stipulation of significant changes in the government of the islanders and in their legal status in the empire. However, Cretan unification remained a key issue for the next forty years.

Greece's first major territorial gains were the regions of Thessaly and Arta in the central mainland. In 1881 the Ottoman Empire ceded most of those regions to Greece as a byproduct of the complex negotiations of the Congress of Berlin to end the RussoTurkish War of 1877. A combination of intense Greek lobbying and Turkish intransigence led to Great Power support for a bilateral treaty transferring the two regions from the Ottoman Empire to Greece.

A second territorial issue of bitter and long-standing importance was the disposition of Macedonia, a territory in which every nationalist group in the Balkans claimed a vital interest. Beginning in the late nineteenth century, efforts to impose either Greek or Slavic culture in Macedonia led to terrorist violence and atrocities and a perpetually volatile situation. Perceiving Macedonia as an essential element of the Megali Idea, Greece held vehemently to its claims, first against the Ottoman Empire and then against other Balkan nations. Elements of this policy remain in force today.