What little is known about the mysterious Jacopo di Poggibonsi is mostly derived from Giorgio Vasari's Lives of the Artists, but some events have been pieced together through archival sources. In 1418, Jacopo is born to Caterina Casazza and Antonio di Poggibonsi. Antonio is a silversmith, and Caterina is the daughter of a farmer from just outside the neighboring village of Staggia . Tragically, Jacopo's mother dies during childbirth, leaving Antonio with their only child. Because of this maternal void in Jacopo's life, the "Madonna and Child" image appears again and again throughout his oeuvre as a memorial to his lost mother.

Virgin and Child Jacopo's earliest known work

In 1430, Antonio meets Cennino d'Andrea Cennini, a native of Colle di Val d'Elsa working in Florence, while Cennini is working on the frescoes of the Life of St. Stephen in the Franciscan convent of San Lucchese, just outside Poggibonsi. Having urged Jacopo from a very young age to develop his artistic abilities and carry on the family tradition, Antonio sends Jacopo to Florence the following year to begin an apprenticeship with Cennini. Cennini's own master had been Agnolo Gaddi, who had been trained by his father Taddeo Gaddi, a pupil of Giotto, making Jacopo the last in a long line of artists in the Giottesque tradition. Cennini's fresco cycle of the Life of St. Stephen appears in the Basilica of San Lucchese just outside Poggibonsi. Other works attributed to him include the Birth of the Virgin (Siena, Pinacoteca Nazionale), a badly damaged street tabernacle of the Virgin and Child (Colle di Val d'Elsa, Via del Castello), and two panels of a polyptych, of Saints Augustine and Gregory (Berlin, Gemäldegallerie). However, Cennini's most important contribution to Renaissance art remains his Il Libro dell'Arte (The Craftsman's Handbook), a technical treatise, written in 1390, intended for artists.

In his handbook, Cennini describes the motivations of many blooming artists of the period. He describes Jacopo as an artist being drawn "through natural enthusiasm" to "enter the profession." Cennini notes that:

...through this delight, they come to want to find a master; and they bind themselves to him with respect for authority, undergoing an apprenticeship in order to achieve perfection in all this. There are those who pursue it, because of poverty and domestic need, for profit and enthusiasm for the profession too; but above all these are to be extolled the ones who enter the profession through a sense of enthusiasm and exaltation. (Cennini, 14)

You, therefore, who with lofty spirit are fired with this ambition and are about to enter the profession, begin by decking yourselves with this attire: Enthusiasm, Reverence, Obedience, and Constancy. And begin to submit yourself to the direction of a master for instruction as early as you can; and do not leave the master until you have to. (Cennini, 14-15)

In 1438, at the age of twenty, Jacopo meets Fillipo Lippi, who has been a friar at Santa Maria del Carmine for ten years. Upon their meeting, Jacopo could not have foreseen the intense rivalry that would soon form between he and Lippi, as initially, they were more than pleasant acquaintances.

After working in the midst of Lippi, Jacopo begins to believe that Lippi is much more talented than he is. This greatly disturbs Jacopo, as he had been quite confident in his artistic ablities. He suffers through a period of withdrawal and depression at the prospect of having his talent overshadowed by Lippi.

Luck befalls the distraught Jacopo the following year. Upon his visit to Rome in 1439, Jacopo meets Benedetto di Sale and falls deeply and passionately in love with him. They agree to meet at Lorenzo Ghiberti's famous bronze doors of the Baptistry the following week. This newfound relationship alleviates some of Jacopo's anxiety and depression. The more time they spend together, the more Benedetto seems to fill the emotional void left by the death and absence of Jacopo's mother.

In 1440, by the age of twenty-two, Jacopo is working on his own and continues to correspond secretly with Benedetto di Sale, the two making several clandestine rendezvous to Rome. However, Jacopo is still not over the prospect of Lippi becoming greater than he. Thus, he harbors a growing envy towards Lippi, ten years his elder, and resents Lippi's natural talent. In a desperate, jealous rage, Jacopo attempts to redeem himself and begins to take artistic liberties with Lippi's work, claiming them to be his own.

In 1447, Jacopo, age twenty-nine, is discovered by Cosimo de' Medici to be copying several figural types in Lippi's Adoration in the Medici Palace. Although Lippi is considered by most to be a more talented artist, he is quite upset with Jacopo's renditions and does not especially appreciate Jacopo's appropriation of his own figures. During mass the next Sunday, Lippi stands on a pew and proclaims to the entire parish that Jacopo is a "leech."

As Lippi is working for the Medici, Jacopo is painting for the Strozzi family, another prominent family in Florence. The tension between these two Florentine families certainly exacerbated the artists' rivalry. Lippi, with the help of Cosimo de' Medici, begins investigating the private life of Jacopo in order to expose him as a fraud and to take away from his growing fame. Lippi discovers Jacopo's torrid affair with Benedetto, and has Cosimo exile Jacopo on the charge of sodomy. Cosimo threatens that if Jacopo either continues any copying activity or corresponds with Benedetto, then he will suffer "pain of death."

Humiliated and fearful, Jacopo returns to his native Poggibonsi to live in a state of secrecy. Benedetto, under the force of the Medici, returns to his own home in the hills surrounding Rome, and the lovers are forbidden from communicating.

Though Jacopo continues to work in Poggibonsi during the last few years of the 1440's, the threats from Lippi continue. Jacopo lives in solitude, distraught at being separated from Benedetto. Around 1448, despite Lippi's threats, Jacopo and Benedetto begin corresponding again.

Jacopo's frustrations with the state of his life are felt in his last two works, a Self-Portrait, and a sketch of a young man believed to be Benedetto. In 1449, Jacopo's Adoration appears on the Florentine art market and fetches a large sum. Envious, Lippi is outraged and orders a gang of thugs to locate Jacopo's residence in the Tuscan countryside. Not only do they discover a third Adoration, but, they find the recent correspondence between Jacopo and Benedetto, correspondence indicating that Jacopo has not complied with either of their demands. Days later, Jacopo, at the young age of thirty-one, is found murdered in his bed, Bendetto's body, covered in self-inflicted knife wounds, lying lifeless next to his.