The death of Cardinal Beaton left Scotland and the Church without a skilled and resolute defender. His successor in the see, Archbishop Hamilton, a half-brother of the Regent, was more licentious than the Cardinal (who seems to have been constant to Mariotte Ogilvy), and had little of his political genius. The murderers, with others of their party, held St Andrews Castle, strong in its new fortifications, which the queen-mother and Arran, the Regent, were unable to reduce. Receiving supplies from England by sea, and abetted by Henry VIII., the murderers were in treaty with him to work all his will, while some nobles, like Argyll and Huntly, wavered; though the Douglases now renounced their compact with England, and their promise to give the child queen in marriage to Henry's son. At the end of November, despairing of success in the siege, Arran asked France to send men and ships to take St Andrews Castle from the assassins, who, in December, obtained an armistice. They would surrender, they said, when they got a pardon for their guilt from the Pope; but they begged Henry VIII. to move the Emperor to move the Pope to give no pardon! The remission, none the less, arrived early in April 1547, but was mocked at by the garrison of the castle.

The garrison and inmates of the castle presently welcomed the arrival of John Knox and some of his pupils. Knox (born in Haddington, 1513-1515?), a priest and notary, had borne a two-handed sword and been of the body-guard of Wishart. He was now invited by John Rough, the chaplain, to take on him the office of preacher, which he did, weeping, so strong was his sense of the solemnity of his duties. He also preached and disputed with feeble clerical opponents in the town. The congregation in the castle, though devout, were ruffianly in their lives, nor did he spare rebukes to his flock.

Before Knox arrived, Henry VIII. and Francis II. had died; the successor of Francis, Henri II., sent to Scotland Monsieur d'Oysel, who became the right-hand man of Mary of Guise in the Government. Meanwhile the advance of an English force against the Border, where they occupied Langholm, caused Arran to lead thither the national levies. But this gave no great relief to the besieged in the castle of St Andrews. In mid-July a well-equipped French fleet swept up the east coast; men were landed with guns; French artillery was planted on the cathedral roof and the steeple of St Salvator's College, and poured a plunging fire into the castle. In a day or two, on the last of July, the garrison surrendered. Knox, with many of his associates, was placed in the galleys and carried captive to France. On one occasion the galleys were within sight of St Andrews, and the Reformer predicted (so he says) that he would again preach there-as he did, to some purpose.

But the castle had not fallen before the English party among the nobles had arranged to betray Scottish fortresses to England; and to lead 2000 Scottish “favourers of the Word of God” to fight under the flag of St George against their country. An English host of 15,000 was assembled, and marched north accompanied by a fleet. On the 9th of September 1547 the leader, Somerset, found the Scottish army occupying a well-chosen position near Musselburgh: on their left lay the Firth, on their front a marsh and the river Esk. But next day the Scots, as when Cromwell defeated them at Dunbar, left an impregnable position in their eagerness to cut Somerset off from his ships, and were routed with great slaughter in the battle of Pinkie. Somerset made no great use of his victory: he took and held Broughty Castle on Tay, fortified Inchcolme in the Firth of Forth, and devastated Holyrood. Mischief he did, to little purpose.

The child queen was conveyed to an isle in the loch of Menteith, where she was safe, and her marriage with the Dauphin was negotiated. In June 1548 a large French force under the Sieur d'Essé arrived, and later captured Haddington, held by the English, while, despite some Franco-Scottish successes in the field, Mary was sent with her Four Maries to France, where she landed in August, the only passenger who had not been sea-sick! By April 1550 the English made peace, abandoning all their holds in Scotland. The great essential prize, the child queen, had escaped them.

The clergy burned a martyr in 1550; in 1549 they had passed measures for their own reformation: too late and futile was the scheme. Early in 1549 Knox returned from France to England, where he was minister at Berwick and at Newcastle, a chaplain of the child Edward VI., and a successful opponent of Cranmer as regards kneeling at the celebration of the Holy Communion. He refused a bishopric, foreseeing trouble under Mary Tudor, from whom he fled to the Continent. In 1550-51 Mary of Guise, visiting France, procured for Arran the Duchy of Châtelherault, and for his eldest son the command of the Scottish Archer Guard, and, by way of exchange, in 1554 took from him the Regency, surrounding herself with French advisers, notably De Roubay and d'Oysel.