Marcantonio Colonna was born in Lanuvio (a town called at that time Civita Lavinia) by Ascanio Colonna, second duke of Paliano and count of Tagliacozzo (brother of the poet Vittoria Colonna) and Giovanna d'Aragona, nephew of King Ferdinando I of Naples; he was awarded the knighthood of the Order of the Golden Fleece.
Disowned by his father for rebellion, despite being the only living male heir, he managed to regain possession of the Colonnese domains only after about a decade in 1562, thanks to the support of Pope Pius IV, having to sell some feuds including Nemi, Ardea and Civita Lavinia to restore the financial crisis left by Ascanio.
On the occasion of the war of Siena (1553-1554) he was appointed commander of the Spanish cavalry and captain general of the army.
To take away the Duchy of Paliano, Pope Paul IV waged a war against the king of Spain, king of Naples, which ends with the treatise of Cave. On the death of Paul IV, Marcantonio Colonna returned to his feuds, except Paliano, who recovered only under Pius V, who in 1569 raised it to a principality.
In 1570 he was appointed captain general of the papal fleet by Pope Pius V, while the following year Don Juan of Austria named him Captain General of the Allied fleet in the war against Muslims.
The Colonna was one of the main protagonists of the battle of Lepanto (1571). The year before the clash played a decisive diplomatic role: he prepared the preparations and smoothed the mutual distrust between Spaniards and Venetians. In the battle (7 October 1571), the flagship of Colonna and the royal of John of Austria captured the flagship of the Turkish fleet. On his return to Rome, Pope Gregory XIII reconfirmed him captain general of the pontifical fleet and tried to continue the war in the Holy Land on the wave of Lepanto's victory. This intention failed after the signing of the peace between Venice and the Turks (1573), when the Christian League dissolved. The heroic deeds of Marcantonio a Lepanto were the main inspiring reason for the pictorial apparatus of the Galleria Colonna built about a century later in the family palace in Rome.
He stayed for a long time in Avezzano where he had built a still existing fountain. In the city he was very much loved. Here in 1575 he raised the castle built by the Orsini family, built a loggia that overlooked Lake Fucino, transformed the park behind it into the Italian garden and had a new portal next to the ogival one of the Orsini with inscription above it. memory of the victory at Lepanto.
Marcantonio Colonna was also lord of Marino. The battle of Lepanto was of enormous importance for the people of the marines, so much so that Marino is still remembered inside the local Grape Festival, the profane feast that over the last century has been superimposed on the religious festival established by Pope Pius V following the victory against the Turks, in honor of Our Lady of the Rosary, under whose protection the naval expedition had been placed. The Grape Festival, not by chance, is held every year in Marino on the first Sunday of October.
On January 4, 1577, Philip II of Spain named him Viceroy of Sicily. He instituted a new administrative subdivision of the territory of the Kingdom of Sicily: with the pragmatics of 13 April 1583, in fact decreed the establishment of the Comarche, at whose center there were the 42 state-owned cities. The main functions were administrative, tax collection and population census.
In 1584 he was recalled to Spain, where he died the same year at the age of forty-nine. Later reported in Italy he was buried in the collegiate church of S. Andrea in Paliano.