The Renaissance in Rome occupied a period from the mid-15th to the mid-16th centuries, a period which spawned masters such as Michelangelo and Raphael, who left an indelible mark on Western figurative art. The city had been a magnet for artists wishing to study its classical ruins since the early 15th century. A revived interest in the Classics brought about the first archaeological study of Roman remains by the architect Filippo Brunelleschi and the sculptor Donatello, both Florentines. This inspired a corresponding classicism in painting and sculpture, which manifested itself in the paintings of Masaccio and Uccello. Pisanello and his assistants also frequently took inspiration from ancient remains, but their approach was essentially cataloguing, acquiring a repertoire of models to be exploited later.

In the year 1420, Pope Martin V moved the papal seat back to Rome, ending its long Avignon Papacy or "Babylonian captivity", and the Papal Schism, when several "popes" simultaneously claimed the office. He at once set to work, establishing order and restoring the dilapidated churches, palaces, bridges, and other public structures. For this reconstruction he engaged some famous masters of the Tuscan school, and thus laid the foundation for the Roman Renaissance.

Roman Renaissance art remained largely dependent on artists from further north, above all Florence, until at least the start of the 16th century. Spending by the popes and cardinals considerably increased, tempting many artists to the city.

The 14th century in Rome, with the absence of popes during the Avignon Papacy, was a century of neglect and misery. Rome dropped to its lowest level of population, and those that remained were starving and wretched. Before the return of the papacy, which was repeatedly postponed because of the bad conditions of the city and the lack of control and security, it was first necessary to strengthen the political and doctrinal aspects of the pontiff. When, in 1377, Gregory XI did return to Rome, he found his power more formal than real. It was a city in anarchy because of the struggles between the nobility and the popular faction. There followed four decades of instability, characterized locally by power struggles between the commune and the papacy, and internationally by the great Western Schism. It was finally Martin V of the Colonna family who managed to bring order to the city, laying the foundations of its rebirth.

Pope Martin V was born at Genazzano in 1368. He studied at the University of Perugia, became prothonotary Apostolic under Pope Urban VI, and papal auditor and nuncio at various Italian courts under Pope Boniface IX. On 12 June 1402 he was made Cardinal Deacon of San Giorgio in Velabro. At the Council of Constance he was unanimously elected pope on 11 November 1417, and took the name Martin V in honour of Martin of Tours, whose feast fell on the day of his election. King Sigismund of Germany tried to induce Martin V to stay in Germany while France begged him to come to Avignon, but, rejecting all offers, he set out for Rome on 16 May 1418. After many detours, primarily to cement relations with the Queen of Naples, Bracco di Montone, and others, he arrived on 28 September 1420.

The first work began on the Archbasilica of Saint John Lateran, which has been badly damaged in 1413. In 1421 the church was enriched by a new Cosmatesque floor and the ceiling was repaired, while Gentile da Fabriano received a commission to create a new cycle of frescoes in the right aisle. These were completed by Pisanello after his death in 1427. The basilica also received a new monastery, assigned to the Benedictines. The pavement of the basilica and the columns were designed as signature pieces of the Colonna family.

When Cosimo de' Medici was exiled from Florence, Donatello returned to Rome, remaining until 1433. The two works that testify to his presence in this city, the Tomb of Giovanni Crivelli at Santa Maria in Aracoeli, and the ciborium at St. Peter's Basilica, bear a strong stamp of classical influence. Brunelleschi also returned several times to find inspiration for what was the Renaissance art. While in Florence, Masaccio, first great Italian painter of the Quattrocento, became friends with Brunelleschi and Donatello, and at their prompting in 1423 travelled to Rome, along with his mentor Masolino. From that point he was freed of all Gothic and Byzantine influence, as may be seen in his altarpiece for the Carmelite Church in Pisa. The traces of influences from ancient Roman and Greek art that are present in some of Masaccio's works must also have originated from this trip. Unfortunately, any further innovation was curtailed by Masaccio's premature death at the age of 27.

Eugenius IV (Gabriello Condulmaro, or Condulmerio) was born in Venice in 1388, of a wealthy family. He was nephew to Pope Gregory XII. His service to Pope Martin V was such that he was elected to the papacy on the first scrutiny. However, his papacy was destined to be a stormy one. In 1434, a revolution, fomented by the pope's enemies, broke out in Rome. Eugene escaped down the Tiber to Ostia, where the friendly Florentines were only too happy to receive him. He took up his residence in the Dominican convent of Santa Maria Novella, and sent Vitelleschi, the militant Bishop of Recanati, to restore order in the Papal States. Florence at that time was the centre of literary activity, and clearly influenced the Humanist movement. During his stay in the Tuscan capital, Eugene consecrated the Florence Cathedral, just then finished by Brunelleschi.