When Henry VIII broke from the Catholic Church, he asked James V of Scotland, his nephew, to do the same. James ignored his uncle's request, and further insulted him by refusing to meet with Henry at York. Furious, Henry VIII invaded Scotland. In retaliation for the massive English raid into Scotland, James responded by assigning Lord Maxwell the task of raising an army.

On 24 November 1542, an army of 15,000-18,000 Scots advanced south, Maxwell, though never officially designated commanded of the force, declared he would lead the attack in person. However, he fell sick, never reaching the scene of the battle.

The Scots advance was met at Solway Moss by Sir Thomas Wharton and his 3,000 men. With the earlier loss of Maxwell, Sir James Sinclair declared himself to be James's chosen commander. Unfortunately, the other commanders refused to accept his command and the command structure totally disintegrated.

The battle (better described as a route) on 24 November 1542, was uncoordinated and resulted in few deaths and twelve hundred prisoners, including Sinclair.

James, who was not present at the battle (he remained at Lochmaben), withdrew to Falkland Palace humiliated and ill with fever. He died there two weeks later at the age of thirty. He left behind a six-weeks-old daughter, Mary, Queen of the Scots. The child's nearest male relative was her great uncle, Henry VIII.