The daughter of Fabrizio Colonna, grand constable of the kingdom of Naples, and of Agnese da Montefeltro, Vittoria Colonna was born at Marino fief of the Colonna family in the Alban Hills near Rome.Betrothed when four years old at the insistence of Ferdinand, king of Naples to Francesco Ferrante d'Ávalos, son of the marquis of Pescara, she received the highest education and gave early proof of a love of letters. Her hand was sought by many suitors, including the dukes of Savoy and Braganza, but at nineteen, by her own ardent desire, she was married to d'Ávalos on the island of Ischia.

There the couple resided until 1511, when her husband offered his sword to the League against the French. He was taken captive at the battle of Ravenna (1512) and conveyed to France. During the months of detention and the long years of campaigning which followed, Vittoria and Ferrante corresponded in the most passionate terms both in prose and verse. They saw each other but seldom, for Ferrante was one of the most active and brilliant captains of Charles V; but Vittoria's influence was sufficient to keep him from joining the projected league against the emperor after the battle of Pavia (1525), and to make him refuse the crown of Naples offered to him as the price of his treason.

In the month of November of the same year he died of his wounds at Milan. Vittoria, who was hastening to tend him, received the news of his death at Viterbo; she halted and turned off to Rome, and after a brief stay departed for Ischia, where she remained for several years. She refused several suitors, and began to produce those Rime spirituali which form so distinct a feature in her works. In 1529 she returned to Rome, and spent the next few years between that city, Orvieto, Ischia and other places. In 1537 we find her at Ferrara, where she made many friends and helped to establish a Capuchin monastery at the instance of the reforming monk Bernardino Ochino, who afterwards became a Protestant.

At the age of 46, in 1536, she was back in Rome, where, besides winning the esteem of Cardinals Reginald Pole and Contarini, she became the object of a passionate friendship on the part of 61-year-old Michelangelo. The great artist addressed some of his finest sonnets to her, made drawings for her, and spent long hours in her company. Her removal to Orvieto and Viterbo in 1541, on the occasion of her brother Ascanio Colonna's revolt against Paul III, produced no change in their relations, and they continued to visit and correspond as before. She returned to Rome in 1544, staying as usual at the convent of San Silvestro, and died there on 25 February 1547.

Pietro Bembo, Luigi Alamanni and Baldassare Castiglione were among her literary friends. She was also on intimate terms with many of the Italian Protestants, such as Pietro Carnesecchi, Juan de Valdés and Ochino, but she died before the church crisis in Italy became acute, and, although she was an advocate of religious reform, there is no reason to believe that she herself became a Protestant.

The example of her life helps counteract the impression of the universal corruption of the Italian Renaissance conveyed by such careers as those of the Borgia. Her amatory and elegiac poems, which are the fruits of a sympathetic and dainty imitative gift rather than of any strong original talent, were printed at Parma in 1538; a third edition, containing sixteen of her Rime Spirituali, in which religious themes are treated in Italian, was published at Florence soon afterwards; and a fourth, including a still larger proportion of the pious element, was issued at Venice in 1544.