The area around Esino Lario is surrounded by Alpine mountains, where the karst landscape has produced sink-holes and caves, including the "Icebox of Moncodeno".

The town is located in the Alpine foothills along the north-eastern slopes of Grigna mountain group, 4.3 kilometres (2.7 mi) from the eastern shore of Lake Como.

Geographical features include the Moncodeno, an extensive natural amphitheater located on the north of the northern Grigna at an altitude of between 1,700 metres (5,600 ft) and 2,300 metres (7,500 ft),[5][3] characterised by the presence of a large number of sinkholes (depressions in the ground) and almost 500 caves, formed by the combined action of the karst and erosion by ice that covered the area during the ice ages.

This is due to the phenomenon of inversion (a deviation from the normal atmospheric behaviour, where temperature increases with elevation) frequently observed in midwinter when subtropical high-pressure systems reach northern Italy.

[9] The last glaciation of the quaternary period, the Würm, began 70,000 years ago covering the Como area, and it profoundly changed the land's appearance – shaping the sides of the mountains, creating fertile moraine terraces, leaving many signs of its passage with boulders.

Esino archaeological findings from the 5th century BC show that the area was a crossing point of the main road along the eastern shore of the lake, reaching Colico and the valleys of the Adda and Imera; because of overhanging rocks between Mandello and Bellano, from Lierna the road climbed to Ortanella (currently a frazione of Esino) subsequently declined to Vezio and Bellano.

At the fall of the Western Roman Empire, after the domination of Odoacer and of the Ostrogoths, the Byzantines conquered Italy during the Gothic War.

A contingent from the Byzantine Empire, under the command of magister militum Francione, resisted in Esino Lario for 20 years, avoiding the large reprisals that followed the death of king Alboin and housing wealthy Roman refugees.

A unique representative of both Esino Superiore and Iniferiore took part in the Council of the Community General, which was based in Introbio.

In the first decades of the sixteenth century, the eastern Lario was close to the armies involved in the dispute between France and Spain.

An adventurer, Gian Giacomo Medici, attempted to form a principality on Lake Como and a fleet take long in check the forces of Francesco II Sforza.

At the news of the revolt in Milan in 1848, a group came from Lecco and joined volunteers in the Esino Lario to come to the aid of the Milanese in their Five Days Rebellion.

The first 50 years of the Kingdom of Italy were of economical crisis: wood was no longer required for the coal needed for melting furnaces, and could only be sold afar.

Tourism in Esino Lario began in the late 19th century with scholars coming to study the fossils of Grigne.