Between 1537 and 1540, all of the 300 remaining Catholic monastaries and convents in England were suppressed by Henry VIII's government. A few of them resisted the new order, and several abbots were charged with high treason. Several prominent Catholic aristocrats, such as the Marquess of Exeter, suffered similar fates, being drawn and quartered for their religious allegiances. Henry's campaign against Catholics was accompanied by a fervent campaign against Protestantism. In October 1538, the bishops of England were ordered to search for Anabaptists, members of a small Protestant sect, burn their books, and turn over to the government any who refused to renounce their Anabaptist faith. Several Anabaptist men and women were burned at the stake the following month. November 1538 also saw the show-trial of a prominent Lutheran, John Lambert. Henry himself sat in Lambert's judgment at Whitehall palace, and Lambert was sent to be tortured and burned at the stake.

1540 brought many more trials and executions. In July, Henry staged a sensational trial and execution in the name of the new Church of England. Three Protestants and three Roman Catholics were tried and dragged through the streets of London. The Protestants were burned for heresy, and the Catholics drawn and quartered, the fullest punishment for treason. The most important figure to be sent to the block that summer, however, was Thomas Cromwell, who had once been Henry's most powerful minister. The Anne of Cleves disaster had been Cromwell's downfall, but his death without a trial was made possible, as well, by accusations that he had been using his position as the king's Viceregent to protect Lutherans and to see that the orthodox Six Articles were not enforced throughout the realm. He was condemned as a "detestable heretic" and beheaded for treason. Henry's chief orthodox ministers, the Duke of Norfolk and Bishop Stephen Gardiner, led the successful effort to overthrow Cromwell.

Over the next few years, Henry oversaw many more executions, including that of his fifth wife, Katherine Howard, who was beheaded in 1542. Most of the executions were carried out for religious reasons. In the spring and summer of 1543, Henry issued a prohibition against reading the Bible in English–an activity associated with the spread of Protestant heresy–and a number of Protestants were burned at the stake. Three summers later, a young woman named Anne Askew, was condemned for distributing Protestant literature to the people of London. She was brutally tortured and could hardly stand at her own trial. She was burned at the stake, along with a number of martyrs for the Protestant faith, in June 1546.

The human toll of Henry's religious persecutions was felt in England around the same time of his final wars in France and Scotland. The French war, which ended withe the Peace at Ardres in 1546, was very costly. With only the small city of Boulogne to show for victory, Henry had spent well over two million pounds–an astonishing amount of money in the sixteenth century–in the financing of his last military adventures. Along with all the English lives lost on French battlegrounds, the royal treasury, known as the exchequer, was bankrupt by the end of Henry's reign, and the financial independence of the Crown was essentially destroyed.

With the beheading of Thomas Cromwell and Henry's wife Katherine Howard, the executions of numerous individuals both Protestant and Catholic for their faith, and the expensive, rather futile war in France in the mid-1540s, Henry firmed up his historical reputation as a great tyrant. In examining the later years of his reign, destruction seems to be the common denominator in so many of Henry's policies and actions: destruction of the monastaries, destruction of the newly arrived Protestant religion and the lives of its adherents, destruction of his wives and of a succession of his ministers, and finally the destruction of the royal treasury.

Henry was no doubt feared as a tyrant by those who knew him and by those who swore allegiance to him from afar as their king. The royal household was full of intrigue and fear. One statement uttered that could have been construed as an affront to the king's person could mean the end of a career, and courting the king's wrath–as Cromwell did when he brought Anne of Cleves to England–could mean the end of one's life. Cromwell was not even allowed to stand trial in his own defense, but instead had his fate sealed in Parliament with a Bill of Attainder. It is ironic that Cromwell–who had been so important to Henry in the years of the break with Rome and who had been instrumental in the executions of men such as Sir Thomas More–was hurried away to his own execution by the same powers he had helped to strengthen.

Through all of these unfortunate events, Henry himself remained convinced of his personal righteousness. With equal zeal, Henry wished to stamp out both Popery, as Roman Catholicism was called by its enemies, as well as Protestantism. The test of a heretic usually concerned the doctrine of Transubstantiation. Near the time he was burning Protestants and beheading Catholics for treason, Henry proudly sent the Catholic Emperor Charles V a copy of the religious primer that was used throughout England to teach the doctrines of its new Church. The orthodox doctrine of Transubstantiation figured prominently in the text, and Henry wanted Charles to see it, so that he could see how the Church of England was orthodox, even as it rejected Popery.

Henry's ruthless actions in the name of the Church of England can be somewhat counterbalanced by the conviction of many loyal to the new regime that the changes, both religious and political, were of the greatest importance to England and occasionally called for strong-armed enforcement. The draining of the royal treasury, however, and the loss of life in France for the sake only of Boulogne, seem to merit less understanding. The war in France was carried out largely because of Henry's desire for a sort of "last-hurrah" on the continent: Boulogne was of very little strategic importance, and the war itself was essentially a futile attempt to win a bit of personal glory for Henry in his old age. It cost Henry popularity back home in England, though the success of his armies in Scotland was able to offset the effect.