James was the son of James III and Margaret of Denmark, probably born in Stirling Castle. As heir apparent to the Scottish crown, he became Duke of Rothesay. In 1474, his father arranged his betrothal to Princess Cecily of England. His father was not a popular king and faced two major rebellions during his reign. The marriage negotiations and dowry payments led to the invasion of Scotland and capture of Berwick in 1482 by his uncle Alexander, Duke of Albany and Richard, Duke of Gloucester while James remained at Stirling. James III's army rebelled against him and the English army reached Edinburgh. During the second rebellion, the rebels set up the 15-year-old James as their nominal leader. His father was killed fighting rebels at the Battle of Sauchieburn on 11 June 1488, and James took the throne and was crowned at Scone on 24 June. When he realised the indirect role which he had played in the death of his father, he decided to do penance for his sin. From that date on, he wore a heavy iron chain cilice around his waist, next to the skin, each Lent as penance, adding every year extra ounces.

When war broke out between England and France as a result of the Italian Wars, James found himself in a difficult position as his obligations under the Auld Alliance with France conflicted with the treaty made with England in 1502. The new king of England, Henry VIII, attempted to invade France in 1513, and James reacted by declaring war on England. Pope Leo X sent a letter to James threatening him with ecclesiatical censure for breaking peace treaties on 28 June 1513, and subsequently James was excommunicated by Cardinal Christopher Bainbridge. James summoned sailors and sent the Scottish navy, including the Great Michael to join the ships of Louis XII of France.[17] Hoping to take advantage of Henry's absence at the siege of Thérouanne, he led an invading army southward into Northumbria, only to be killed, with many of his nobles and common soldiers, at the disastrous Battle of Flodden on 9 September 1513, ending Scotland's land-based involvement in the War of the League of Cambrai. In his otherwise flattering portrait of James Pedro de Ayala had cast doubt on James's ability as a military commander, portraying him as impetuous on the battlefield and prone to foolhardiness; He is courageous, even more so than a king should be. I am a good witness of it. I have seen him often undertake most dangerous things in the last wars. On such occasions he does not take the least care of himself. He is not a good captain, because he begins to fight before he has given his orders. He said to me that his subjects serve him with their persons and goods, in just and unjust quarrels, exactly as he likes, and that therefore he does not think it right to begin any warlike undertaking without being himself the first in danger. His deeds are as good as his words.[18] A body, thought to be that of James, was recovered from the battlefield and taken to London for burial. James had been excommunicated, and although Henry VIII had obtained a breve from the Pope on 29 November 1513 to have the King buried in consecrated ground at St. Pauls, the embalmed body lay unburied for many years at Sheen Priory in Surrey.[19] The body was lost after the Reformation. John Stow claimed to have seen it, and said the king's head (with red hair) was removed by a glazier and eventually buried at St Michael Wood Street.[20] James's bloodstained coat was sent to Henry VIII (then on campaign in France) by his queen, Catherine of Aragon.[21] Erasmus provided an epitaph for the King in his Adagia. Later, in 1533, he wrote to James V of Scotland pointing out this essay on duty under the adage Spartam nactus es, (You who were born to Sparta shall serve her), on the subject of the Flodden campaign and the death of James and his son, Alexander.[22]