The latter half of the 15th century saw the seat of the Italian Renaissance move to Rome from Florence. The Papacy wanted to equal and surpass the grandeur of other Italian cities and to this end created ever more extravagant churches, bridges, squares and public spaces, including a new Saint Peter's Basilica, the Sistine Chapel, Ponte Sisto (the first bridge to be built across the Tiber since antiquity), and Piazza Navona. The Popes were also patrons of the arts engaging such artists as Michelangelo, Perugino, Raphael, Ghirlandaio, Luca Signorelli, Botticelli, and Cosimo Rosselli.
 
The Tempietto (San Pietro in Montorio), which is an excellent example of Italian Renaissance architecture

The period was also infamous for papal corruption, with many Popes fathering children, and engaging in nepotism and simony. The corruption of the Popes and the extravagance of their building projects led, in part, to the Reformation and, in turn, the Counter-Reformation. Popes, such as Alexander VI, were well-known for their decadence, wild parties, extravagance and immoral lives. However, under these extravagant and rich popes, Rome was transformed into a centre of art, poetry, music, literature, education and culture. Rome became able to compete with other major European cities of the time in terms of wealth, grandeur, the arts, learning and architecture.

The Italian Renaissance in Rome more or less began when the end of the French captivity came in 1377, and the return of the papacy to Rome. Pope Martin V (1417-1431), planned to renew the Roman Catholic Church, and pursue new spiritual and political reforms. Martin V and his successors began to follow these new instructions, and Pope Nicholas V (1447-1455) really began to plan out much of the Renaissance-style urban re-development of the city.

The Renaissance period changed Rome's face dramatically, with works like the Pietà by Michelangelo and the frescoes of the Borgia Apartment, all made during Innocent's reign. Rome reached the highest point of splendour under Pope Julius II (1503-1513) and his successors Leo X and Clement VII, both members of the Medici family. In this twenty-years period Rome became one of the greatest centres of art in the world. The old St. Peter's Basilica built by Emperor Constantine the Great (which by then was in a terrible state) was demolished and a new one begun. The city hosted artists like Ghirlandaio, Perugino, Botticelli and Bramante, who built the temple of San Pietro in Montorio and planned a great project to renovate the Vatican. Raphael, who in Rome became one the most famous painters of Italy creating frescos in the Cappella Niccolina, the Villa Farnesina, the Raphael's Rooms, plus many other famous paintings. Michelangelo started the decoration of the ceiling of the Sistine Chapel and executed the famous statue of the Moses for the tomb of Julius. Rome lost in part its religious character, becoming increasingly a true Renaissance city, with a great number of popular feasts, horse races, parties, intrigues and licentious episodes. Its economy was rich, with the presence of several Tuscan bankers, including Agostino Chigi, who was a friend of Raphael and a patron of arts. Before his early death, Raphael also promoted for the first time the preservation of the ancient ruins. The fight between France and Spain in Europe caused the first plunder of the City in more than one thousand years. In 1527 the Landsknechts of Emperor Charles V sacked the city, putting to an abrupt end the golden age of the renaissance in Rome.