Mary, Queen of Scots fled to England in 1568 after abdicating. In the negotiations that followed between Mary, Elizabeth, Moray, and their various factions, Elizabeth supported initially a scheme to marry Thomas Howard, 4th Duke of Norfolk to the scottish queen. Norfolk eventually warmed to the idea, seeing his own advancement, no matter how unrealistic this was, however he was considered politically naive and easily manipulated.

At this point the marriage manoeuvrings became linked to the growing and widespread aristocratic hostility and resistance to Cecil. Both disgruntled protestant courtiers, such as Leicester and Pembroke, and Catholics, such as Arundel, Northumberland, and Westmorland, sought not only personal advancement but national security. This required improved Anglo-Spanish relations, which had recently deteriorated owing to the devoutly anti-Catholic Cecil's provocative actions, and settlement of the succession. Catholic nobles, especially in the north, favoured a Mary–Norfolk marriage, which would protect their faith and provide a secure succession. There developed a court conspiracy to remove Cecil, but in February 1569 the queen intervened to prevent it. The conspirators had engaged Norfolk's support, because he regarded Cecil's hostility to Mary as a major obstacle, but by May 1569 he had resumed his former friendly relations with the secretary. Leicester, Arundel, and Pembroke, foiled in their attempt to unseat Cecil, turned to promotion of the Mary–Norfolk marriage. Norfolk was now increasingly led by the various designs of Maitland, Moray, and the Scottish go-between, the bishop of Ross, by Leicester, Pembroke, and their go-between, Sir Nicholas Throckmorton, and by Mary through Ross. The problems and obstacles were numerous: Mary's abdication, adultery, complicity in murder, and her current marriage to the earl of Bothwell; the attitude of the Scots to her restoration; and Cecil's implacable hostility.

Increasingly Norfolk, who remained protestant and, as he saw it, a loyal subject, depended on the words and actions of others. Often they failed to confide in him, especially as some of the plans involved collaboration with Spain and even the liberation of Mary Stuart by force. Some of the northern nobles, who favoured the use of force, were hostile towards the duke and sympathetic to Leonard Dacre, who had lost the lawsuit over the family inheritance. In June 1569 Mary responded to the approaches of Leicester and others by giving her consent to a marriage match, however the major stumbling block was obtaining Elizabeth's consent. This was the crucial problem which caused everyone, not just Norfolk, to procrastinate. He looked to Moray in Scotland for action, writing to him on 1 July that he could not ‘with honour proceed further till such time as he should remove all stumbling-blocks to more apparent proceedings’ (Haynes and Murdin, 520). The Scottish regent, however, no longer approved of the marriage scheme and later that month he secured the defeat of an attempt to end Mary's marriage to Bothwell. In England, Leicester, who had previously stressed the need for the public marriage proposal to come from Scotland, agreed to approach the queen on his behalf. He insisted, however, that care must be taken to choose the most favourable opportunity. At a meeting of the privy council in late July from which Cecil was absent, there was overwhelming support for the proposition that Mary should be freed if she married an English nobleman.

Elizabeth eventually saw the double dealing that was taking place and refused to give her consent. Norfolk removed himself from the court and all initially seemed to evaporate, however the northern Earls were far from satisfied. They looked to Norfolk for their lead and when he was placed under virtual house arrest Thomas Percy, 7th Earl of Northumberland and Charles Neville, 6th Earl of Westmorland led an uprising to restore the Roman religion and free both Mary, Queen of Scots and Norfolk.

Marching south the army took Durham, installing a Catholic altar in the Cathedral. They then successively took Staindrop, Darlington, Richmond, and Ripon, establishing the Roman church in each, all areas that had strong Catholic support. Marching on York, they received intelligence that Walter Devereux, Earl of Essex had amassed a sizeable force against them so they turned to Barnard Castle and then Raby Castle, where they were met with resistence. After an 11 day siege they took the castle and moved to Clifford Moor near Weatherby, where their small force of less than 5,000 men had Westmorland begin to lose hope. He slipped away to France, leaving Northumberland and Dacre to face Essex alone with a force of only 3,000. Percy and Dacre were crushed and the rebellion was ended.

Upwards of 60 with noble blood were attainted of treason and executed including Northumberland. Norfolk was kept under house arrest in Howard House for much of the following year, stupidly involving himself in further conspiracy that ultimately led to his execution for the Ridolfi Plot.