Henry VIII of England concluded the Treaty of Westminster, a pledge of mutual aid against the French, with Ferdinand II of Aragon.

The War of the League of Cambrai, sometimes known as the War of the Holy League and several other names, was fought from February 1508 to December 1516 as part of the Italian Wars of 14941559. The main participants of the war, who fought for its entire duration, were France, the Papal States, and the Republic of Venice; they were joined at various times by nearly every significant power in Western Europe, including Spain, the Holy Roman Empire, England, the Duchy of Milan, the Republic of Florence, the Duchy of Ferrara, and the Swiss.

The war started with the Italienzug of Maximilian I, King of the Romans, crossing into Venetian territory in February 1508 with his army on the way to be crowned Holy Roman Emperor by the Pope in Rome. Meanwhile, Pope Julius II, intending to curb Venetian influence in northern Italy, brought together the League of Cambrai an anti-Venetian alliance consisting of him, Maximilian I, Louis XII of France, and Ferdinand II of Aragon which was formally concluded in December 1508. Although the League was initially successful, friction between Julius and Louis caused it to collapse by 1510; Julius then allied himself with Venice against France.

The VenetoPapal alliance eventually expanded into the Holy League, which drove the French from Italy in 1512; disagreements about the division of the spoils, however, led Venice to abandon the coalition in favor of an alliance with France. Under the leadership of Francis I, who had succeeded Louis on the throne of France, the French and Venetians would regain the territory they had lost in a campaign culminating in the Battle of Marignano in 1515; the treaties of Noyon (August 1516) and Brussels (December 1516), which ended the war the next year, would essentially return the map of Italy to the status quo of 1508.

Henry VIII (28 June 1491 – 28 January 1547) was King of England from 22 April 1509 until his death in 1547. Henry is best known for his six marriages, and for his efforts to have his first marriage (to Catherine of Aragon) annulled. His disagreement with Pope Clement VII about such an annulment led Henry to initiate the English Reformation, separating the Church of England from papal authority. He appointed himself Supreme Head of the Church of England and dissolved convents and monasteries, for which he was excommunicated. Henry is also known as "the father of the Royal Navy," as he invested heavily in the navy, increasing its size from a few to more than 50 ships, and established the Navy Board.Domestically, Henry is known for his radical changes to the English Constitution, ushering in the theory of the divine right of kings in opposition to Papal supremacy. He also greatly expanded royal power during his reign. He frequently used charges of treason and heresy to quell dissent, and those accused were often executed without a formal trial by means of bills of attainder. He achieved many of his political aims through the work of his chief ministers, some of whom were banished or executed when they fell out of his favour. Thomas Wolsey, Thomas More, Thomas Cromwell, Richard Rich, and Thomas Cranmer all figured prominently in his administration.

Henry was an extravagant spender, using the proceeds from the dissolution of the monasteries and acts of the Reformation Parliament. He also converted the money that was formerly paid to Rome into royal revenue. Despite the money from these sources, he was continually on the verge of financial ruin due to his personal extravagance, as well as his numerous costly and largely unsuccessful wars, particularly with King Francis I of France, Holy Roman Emperor Charles V, King James V of Scotland and the Scottish regency under the Earl of Arran and Mary of Guise. At home, he oversaw the legal union of England and Wales with the Laws in Wales Acts 1535 and 1542, and he was the first English monarch to rule as King of Ireland following the Crown of Ireland Act 1542.

Henry's contemporaries considered him to be an attractive, educated, and accomplished king. He has been described as "one of the most charismatic rulers to sit on the English throne" and his reign has been described as the "most important" in English history. He was an author and composer. As he aged, he became severely overweight and his health suffered. He is frequently characterised in his later life as a lustful, egotistical, paranoid and tyrannical monarch. He was succeeded by his son Edward VI.