1592, May 7
A plague epidemic begins, killing around 3,000 people until its end in September 1593.
1566, March 28
The founding of Malta's new capital city, Valletta. A general strengthening of Malta's fortifications is undertaken.
1565, September 13
Turkish forces retreat from Malta.
1565, September 7
Don Garcia's reinforcements, known as the Grande Soccorso ('great relief'), finally arrive.
1565, July 12
Senglea is besieged.
1565, July 9
Reinforcements sent by Viceroy Don García de Toledo fail to make harbour, as a result of the fall of Fort St. Elmo, and return to Sicily.
1565, July 8
The Turkish forces are reinforced with the arrival of 29 vessels and 2,500 warriors accompanied by the Bey of Algiers.
1565, July 3
The Turkish fleet is transported on rollers, overland, from Marsamxett Harbour to Grand Harbour, in preparation for an assault on Senglea. (to 12 July)
1565, June 29
Four galleys land in the north of Malta, bringing 600 soldiers, 42 knights, 56 gunners and numerous volunteers, to reinforce the Island's defences; they walk to Mdina by night, and then on to Birgu the following morning.
1565, June 23
Turkish commanders order all the dead Knights found in St. Elmo to be beheaded; their mutilated bodies are floated across Grand Harbour on planks towards the bastions of Senglea and Birgu.
1565, June 23
Fort St. Elmo falls to the Turks.
1565, May 20
The Turkish fleet anchors at Marsaxlokk, moved to Żejtun and sets up camp at Marsa.
1565, May 19
A storm prevents the Turkish fleet from landing at Marsaxlokk; the vessels are sheltered in Ġnejna Bay and at Għajn Tuffieħa.
1565, May 18
Ottoman armada sighted off the coast of Malta, signalling the start of the Great Siege of Malta.
1565, April 16
Evacuation to Sicily of 'a great number of people' from Malta, including large numbers of Maltese nobility, in anticipation of the imminent invasion. (to 13 May)
1565, March 30
The Spanish Viceroy of Sicily, Don García de Toledo y Osorio, tours the Island's fortifications; he promises the Knights that in the coming invasion they need only hold out until June, when he would bring his armada back to assist Malta.
1565, March 30
Ottoman fleet leaves Constantinople for Malta; Queen Elizabeth remarks: 'If the Turks should prevail against the Isle of Malta, it is uncertain what further peril might follow to the rest of Christendom.'
1564, December
The Ottoman war council in Constantinople decrees that Malta is to be invaded and conquered.
1561
The Holy Inquisition is established in Malta. Domenico Cubelles is the first Inquisitor.
1560
The Knights of Malta escalate their corsairing activities in the western Mediterranean. (to 1565)