Since the middle of the 13th century the Borgia family took up residence in Xátvia, a town at the border of the kingdom of Valencia which was only taken back from the Moors shortly before. The original name "de Borja" indicates that the family origniated in the old Aragonese stronghold by the same name. It was the meteoric rise of Alonso de Borja (1378-1458) which also elevated the family. Coming from an impoverished collateral line of the family, Alonso took up a career as a cleric not through theological but legal studies. Subsequently he taught at the University of Lérida where he was made canon by Antipope "Benedict XIII". In the service of King Alfonso V of Aragon, he became a gifted diplomat. In the curia, he assisted in the abdication of the antipope "Clement VIII" and helped to bring the religious schism to an end. Due to this pope Martin V enfeoffed him with the diocese of Valencia. As a side effect to this elevation the main line of the family agreed on a marriage between their decendent Joffre Borgia and Alonso's older sister Isabella. This marriage produced among other children Rodrigo Borgia (1431-1503).

On another diplomatic mission Alonso succeeded in reconciling King Alfonso V with Pope Eugen IV after his conquest of the kingdom of Naples. This took away one of the mainstays of the schismatic Council of Basel and allowed the pope to return to Rome. Eugene IV thereupon made him cardinal and invited him to join the papal curia in 1444. Until his election that made him pope Calixtus III in the conclave of 1455, he occupied himself again mainly with legal studies. There were two reason for the elevation of the first Spanish pope in over a thousand years: His old age of 77 (so that a new conclave could be expected soon) and his origin being in the homeland of the Reconquista, which led to expect firm action against Turkish expansion politics. While he made good on these promises, the Roman families were put off by his personnel policy as he gave away lucrative positions to other Catalans, especially relatives. He made two of his nephews, Rodrigo and Luis-Juan, cardinal in 1456 and Rodrigo's brother Pedro Luis leader of the papal armies. Therefore his death in 1458 was the signal for popular outbreaks against the hated Catalans led especially by the Orsini family.

Holding the lucrative position of vice chancellor and many benefices (among them the diocese of Valencia), Rodrigo Borgia made a fortune with the intent of eventually becoming pope himself. He lived in a quasi-marital relationship with Vanozza Cattanei, mother of four of his eight legitimized children. In the 1470s he acquired the fiefdom of Gandia and a betrothal to the king's niece Maria Enriquez for his eldest son Pedro Luis by procuring the marital dispensation for Isabella of Castille and Ferdinand of Aragon. After Pedro Luis' untimely death, land and wife went to his younger brother Juan. Rodrgio also forged new alliances in the curia by marrying his eldest daughter Girolama to a member of the Cesarini family. Later his ambitions focused on his children Cesare, Juan, Lucrezia and Joffre. In 1494 Rodrigo Borgia became pope and called himself Alexander VI. His pontificate was marked by the investiture controversy regarding the kingdom of Naples, the weakening of the Roman nobility and the loss of power of feoffees such as Caterina Sforza (Forlì) and Astorre Manfredi (Faenza) in the Romagna. For all his faults and alleged vices, Alexander VI was in a theological-dogmatical sense one of the most conservative and pious popes of his time. This can be seen by the traditionally religious frescoes in the Borgia apartments of the Vatican.

After Alexander VI's death in 1503 his son Cesare, previously made Duke of the Romagna, couldn't keep his power in Italy. He died four years later after long Spanish imprisonment and a short time in the service of his brother-in-law, King John of Navarre. Only Rodrigo's daughters Isabella and Lucrezia as well as his son Joffre were spared from the repercussions of family's disintegration of power. Of his children's decendents, Juan's first son married Juana, a granddaughter of King Ferdinand of Aragon, and was elevated in the highest circles of the Spanish nobility. Their first son Francisco Borgia (1510-1572) joined the Jesuit Order after becoming a widower. He was voted general of the Order and canonized due to his impeccable moral conduct in 1671. Isabella's great-great grandson Giovanni Battista Pamphilj became pope Innocent X in 1644 and went down in history as one of the most politically shrewd pontiffs of the era, who much increased the temporal power of the Holy See. In the 1600s the Borgia's influence on the Spanish court had reached its climax: The diocese of Toledo (the richest in all Christendom) was acquired by Cardinal Gasparo Borgia (1582-1645). He is most known for his unbending views in the trial against Galilei (1633). Before that he had threatened Cardinal Richelieu in a heated consistory with persecution as a heretic. Two more decendents were made cardinal but after that the decline of the family was unstoppable.