Giampaolo Baglioni was born in Perugia around 1470. Following the family tradition, he became a "condottiere", or a solder of fortune, and since 1493 he was for several years at the service of the Florentines. When the government of Perugia was seized by Girolamo della Penna and Carlo Baglioni, Giampaolo went to Vitellozzo Vitelli who was at Marciano, not far from Perugia, and with the help of Vitellozo was able to put together a group of soldiers and regained Perugia. In 1500 he was at the service of Pope Alexander VI, and helped the Pope's son, Cesare Borgia, the Duke Valentino, in the fight against the Colonnas. He was then offered the position of Captain General of the Siena troops, but Giampaolo refused. He also refused an offer from Florence, and went to work with Cesare Borgia at the assault of Faenza. Later, in 1501, he participated with the Valentino in the expedition against Piombino. Giampaolo was then called by Piero de' Medici and Pandolfo Petrucci to take part in their attempts against Florence. But after Duke Valentino's occupation of Urbino, Giampaolo realized that the ambitious plans of the Pope's son would one day be fatal also to Perugia. He returned home and tried to organize the resistance of the lords of central Italy whose territories were menaced by Cesare Borgia.
It was Giampaolo who organized the Diet of La Magione, and on November 9, 1502, he presided over that meeting. It seemed that a definite plan had been reached with all the participantsthe Baglionis, Cardinal Giambattista Orsini, Francesco Orsini Duke of Gravina, Paolo Orsini, Ermes Bentivoglio, Oliverotto da Fermo, Antonio Giordano da Venafro for Pandolfo Petrucci, Prince of Siena, and Ottaviano Fregoso for Guidobaldo da Montefeltro, Duke of Urbino. However, at the end of November a new meeting was held in Chianciano, and the Orsinis, Bentivoglio and Petrucci were for a plan of compromise with Cesare Borgia. Giampaolo and Vitellozzo Vitelli tried in vain to change their mind. Giampaolo anticipated and escaped Cesare Borgia's deception and slaughter of Sinigallia on December 31, 1502, although he had to leave Perugia. He went to Florence, but was able to return to Perugia in 1503, after Pope Alexander's death. Under the new Pope, Julius II, Giampaolo seeked the protection of Guidubaldo da Montefeltro, and thus he obtained from the Pope to keep his territories and to live in Perugia. At the death of Julius II in 1513, the new elected pope, Leo X, was a de' Medici. In 1516 Giampaolo became Lorenzo de' Medici's counselor in the war against Urbino. The war was proceeding slower than expected, and Giampaolo was accused of plotting with Francesco Maria della Rovere, Duke of Urbino. There was a preoccupation that an understanding between Giampaolo and the Duke of Urbino would create an unfavorable situation for Lorenzo de' Medici, who pressed the Pope on this point. As a consequence Pope Leo X decided to eliminate the lord of Perugia. So he called Giampaolo to Rome several times. Finally in March 1520 Giampaolo went to Rome to see the Pope, but was never allowed to see His Holiness. He was instead imprisoned in Castel Sant'Angelo, and a couple of months later, on the night of June 11, 1520, was decapitated