The First Italian War, or Charles VIII's Italian War, was the opening phase of the Italian Wars. The war pitted Charles VIII of France, who had initial Milanese aid, against the Holy Roman Empire, Spain and an alliance of Italian powers led by Pope Alexander VI, known as the League of Venice.

This is an overview of notable events including battles during the war.

Pope Innocent VIII, in conflict with King Ferdinand I of Naples over Ferdinand's refusal to pay feudal dues to the papacy, excommunicated and deposed Ferdinand by a bull of 11 September 1489. Innocent then offered the Kingdom of Naples to Charles VIII of France, who had a remote claim to its throne because his grandfather, Charles VII, King of France, had married Marie of Anjou of the Angevin dynasty, the ruling family of Naples until 1442. Innocent later settled his quarrel with Ferdinand and revoked the bans before dying in 1492, but the offer to Charles remained an apple of discord in Italian politics. Ferdinand died on 25 January 1494 and was succeeded by his son Alfonso II.

A third claimant to the Neapolitan throne was René II, Duke of Lorraine. He was the oldest son of Yolande, Duchess of Lorraine (died 1483), the only surviving child of René of Anjou (died 1480), the last effective Angevin King of Naples until 1442. In 1488 the Neapolitans had already offered the crown of Naples to René II, who set an expedition to gain possession of the realm, but he was then halted by Charles VIII of France, who intended to claim Naples himself. Charles VIII was arguing that his grandmother Marie of Anjou, the sister of René of Anjou, had a closer connection than Rene II's mother Yolande, the daughter of René of Anjou, and therefore he came first in the Angevin line of Neapolitan succession.^{[citation needed]}

Casus belli of the conflict was the rivalry that arose between the Duchess of Bari, Beatrice d'Este, wife of Ludovico Sforza, known as the Moor, and the Duchess of Milan, Isabella of Aragon, wife of Gian Galeazzo, who both aspired to control of the Duchy of Milan and to the hereditary title for their children: since 1480 Ludovico Sforza ruled that duchy as regent of his little nephew Gian Galeazzo, not being therefore duke by right, but only de facto. The situation remained calm until 1489, when the marriage between Gian Galeazzo and Isabella of Aragon, granddaughter of King Ferrante of Naples as the daughter of Alfonso Duke of Calabria, took effect. Isabella immediately realized that all power was reduced to the hands of Louis and suffered from the ineptitude of her husband, listless and totally disinterested in the government; nevertheless he endured in silence until, in 1491, Ludovico married Beatrice d'Este, daughter of the Duke of Ferrara Ercole I d'Este and cousin of Isabella on her mother's side. Determined and ambitious young woman, Beatrice was soon associated by her husband with the government of the state, nor Isabella, "angry and desperate for envy", could bear to see herself surpassed in all honors by her cousin.

The Duchy of Milan was at the time the richest state in Italy after the Republic of Venice and its treasury amounted to as many as one and a half million ducats. In December Ludovico led his wife to see him and promised her that, if he gave him a son, he would make her a lady and mistress of everything; conversely, dying him, she would have very little left. Already in January 1492 Beatrice predicted to the Florentine ambassador that within a year she and her husband would be dukes of Milan, and the hostility between the two cousins became so intense that in February Ludovico, strong of some rumors coming from France, accused King Ferrante of having spurred Charles VIII to wage war against him, in order to free Gian Galeazzo from his tyranny; he also refused to meet the Neapolitan orator, except behind a very large armed escort, claiming that he was sent by the Duke of Calabria to assassinate him. To make the suspicions more concrete was added, at the end of the year, the attempted poisoning, perpetrated by Isabella of Aragon rea confesses, against Galeazzo Sanseverino, dear son-in-law and captain general of the Moro, as well as the danger that this was repeated against some other member of the ducal family.

The point of definitive rupture, however, took place in January 1493, with the birth of Hercules Maximilian, eldest son of Moro and Beatrice: the possession of a legitimate descent was what was still missing for the spouses to be able to aspire to the ducal title. Rumors spread that Ludovico intended to appoint his son Count of Pavia – a title belonging exclusively to the heir to the duchy – in place of Isabella's son, Francesco. The latter, feeling threatened, asked for the intervention of her father Alfonso of Aragon, whose impetus was however restrained by the wiser King Ferrante, who repudiated the war by officially declaring: ""if the wife of the Duke of Milan is my nephew, the wife of the Duke of Bari is also my nephew". He, moreover, had been affectively very close to Beatrice, whom until 1485 he had raised as a daughter; he declared that he loved both granddaughters equally and urged them to be prudent, so that the situation remained stable until the king was alive.

In May Ludovico Sforza sent his wife Beatrice as his ambassador to Venice and communicated to the Signoria, through her, some of his secret practices with Emperor Maximilian I of Habsburg to obtain the investiture to the Duchy of Milan, as well as the secret news just communicated to him that Charles VIII, signed the peace with the emperor, was determined to carry out his enterprise against the kingdom of Naples and to appoint Ludovico head and conductor of said enterprise. The spouses therefore wished to know the opinion of the Signoria in this regard, and indirectly asked for its support. The Venetians replied that what was reported was very serious and limited themselves to vague reassurances, keeping out of these maneuvers.