Giuliano was the son of the impoverished Rafaello della Rovere, Pope Sixtus IV's only brother. In 1468 he became a Franciscan, and in 1471 Sixtus IV made him a cardinal. In this office Giuliano displayed all of the attributes of cupidity and corruption of an unscrupulous Renaissance prince. The Pope lavished on him six bishoprics in France and three in Italy along with an abundance of wealthy abbeys and benefices. The Cardinal, who lacked any interest in spiritual pursuits, became an outstanding patron of the arts. He is shown with his protégés in Melozzo da Forlì's superb fresco of Sixtus IV in the Vatican Museum.

After the death of Sixtus IV, for whom Giuliano commissioned a bronze sepulchre by Antonio Pollaiuolo, now in the Vatican Grotto of St. Peter's, the Cardinal's candidate, the weak Innocent VIII, was elected through bribery. When Rodrigo Borgia, elected pope as Alexander VI in 1492, plotted Giuliano's assassination, Giuliano fled in 1494 to the court of Charles VIII of France. He accompanied the French king on his expedition against Naples in the hope that Charles would also depose Alexander VI. After accompanying Charles on his forced return to France, Giuliano took part in Louis XII's invasion of Italy in 1502. Alexander VI twice attempted to seize him.

Following the death of the Borgia pope in 1503, Giuliano returned to Rome, having been 10 years in exile, and, after Pius III's brief pontificate, was, with the liberal help of simony, elected Pope Julius II in October 1503. Immediately after his election he decreed that all future simoniacal papal elections would be invalid and subject to penalty.

Having become an exponent of Italian national consciousness, Julius II proposed to drive the French from Italy, but his second war, which lasted from September 1510 to May 1511, was unsuccessful. Several cardinals defected to Louis XII and called a schismatic council, to which Julius responded by summoning the fifth Lateran Council. After concluding an alliance with Venice and Ferdinand II of Spain and Naples in October 1511, he opened the council in May 1512 at the Lateran Palace. Louis XII had defeated the troops of the alliance at Ravenna in April 1512, but the situation changed when Swiss troops were sent to the Pope's aid. The territories in northern Italy occupied by the French revolted, the French left the country, and the Papal States were augmented by the acquisition of Parma and Piacenza. Toward the end of his life, he viewed with concern the replacement of French by Spanish efforts to attain supremacy in Italy. Julius II was Italy's saviour.

The enduring impact of the life of Julius II stemmed from his gift for inspiring great artistic creations. His name is closely linked with those of such great artists as Bramante, Raphael, and Michelangelo. With his wealth of visionary ideas, he contributed to their creativity. Following an overall plan, he added many fine buildings to Rome and laid the groundwork in the Vatican Museum for the world's greatest collection of antiquities. Among the innumerable Italian churches that benefitted from his encouragement of the arts was Sta. Maria del Popolo in Rome, for which he commissioned Andrea Sansovino to create sepulchres for a number of cardinals and Pinturicchio to paint the frescoes in the apse. Donato Bramante (Bramante, Donato) became the architect of Julius' fortifications in Latium, of the two galleries that form the Belvedere Court, and of other Vatican buildings. Around 1503 the Pope conceived the idea of building a new basilica of St. Peter, the first model of which Bramante created. Its foundation stone was laid on April 18, 1506.

The Pope's friendship with Michelangelo, begun in 1506, was enduring despite recurrent strains imposed on their relations by the two overly similar personalities. Their relationship was so close that the Pope became, in fact, Michelangelo's intellectual collaborator. Of Julius' tomb only the “Moses” in the church of S. Pietro in Vincoli, in Rome, was completed; the Pope is, however, not interred there but in St. Peter's, along with the remains of Sixtus IV. The famous bronze statue of the Pope for the church of S. Petronio in Bologna, completed in 1508, was destroyed in 1511. In 1508 Michelangelo was prevailed upon by Julius to begin his paintings on the ceiling of the Sistine Chapel, which were unveiled in October 1512. The paintings, which represent a climax in Western art, were, in form and conception, a product of the artistic symbiosis of Michelangelo and the Pope.

By 1509 Raphael, introduced to Julius, had begun his masterpieces for the Pope, the frescoes in three rooms of the Vatican (Vatican palace). Spiritual references to the person and the pontificate of Julius II are evident in one of the rooms (the Stanza della Segnatura), where earthly and celestial wisdom are juxtaposed in the “School of Athens” and the “Disputa,” while the beauty of creativity is represented in the “Parnassus.” The theme of another room (the Stanza d'Eliodoro), which could be called a transcendental “political” biography of the Pope, is still more personal. “The Expulsion of Heliodorus from the Temple” symbolizes the expulsion of the French and the subjugation of all the church's enemies, with Julius II depicted witnessing the scene from his portable throne. Closely related to this is the “Liberation of St. Peter,” in which light and darkness serve to symbolize the historic events of the pontificate. The third great fresco in this room, the “Mass of Bolsena,” shows the Pope kneeling, rather than enthroned, in commemoration of his veneration of the corporale (communion cloth) of Bolsena in the cathedral of Orvieto. In addition to these fresco portraits, there is one by Raphael in the Uffizi gallery in Florence, one of the masterpieces of portraiture, which shows the Pope not as the victorious Moses springing to his feet, as Michelangelo portrayed him, but as a resigned, pensive old man at the end of an adventurous, embattled life. Michelangelo's chalk drawing of the Pope in the Uffizi gallery approaches it in quality.

As cardinal, Julius II fathered at least one illegitimate daughter, Felice. He made four members of the Della Rovere family cardinals, only one of whom achieved any importance. From the marriage of the Pope's only brother, Giovanni, to the daughter and heiress of Duke Federigo of Montefeltro descended the dukes of Urbino.

The Pope added wisely to the church's treasures. Although he had little of the priest in him, he was concerned toward the end only with the church's grandeur. He wished for greatness for the papacy rather than for the pope, and he wished for peace in Italy. The Swiss historian Jacob Burckhardt called him the “saviour of the papacy,” because Alexander VI had greatly endangered its existence for the sake of his family interests.

Julius had an extraordinarily violent temper, often lost his self-control, and could be rude and often even vulgar in manner. Yet, apart from the avarice and corruption inherent in his office and time as much as in himself, he was incapable of baseness and vindictiveness and despised informers and flatterers; no one was able to influence his decisions. Everywhere he saw and sought out greatness. He lacked the smooth manners of the servile. His faults arose from his relentless candour and uncontrollable temper. He was called terrible, an epithet suggesting that he was regarded as sublime, even superhuman.