The nine-year-old Edward wrote to his father and stepmother on 10 January 1547 from Hertford thanking them for his new year's gift of their portraits from life.[34] By 28 January 1547, Henry VIII was dead. Those close to the throne, led by Edward Seymour and William Paget, agreed to delay the announcement of the king's death until arrangements had been made for a smooth succession. Seymour and Sir Anthony Browne, the Master of the Horse, rode to collect Edward from Hertford and brought him to Enfield, where Lady Elizabeth was living. He and Elizabeth were then told of the death of their father and heard a reading of the will.[35] The Lord Chancellor, Thomas Wriothesley, announced Henry's death to parliament on 31 January, and general proclamations of Edward's succession were ordered.[36] The new king was taken to the Tower of London, where he was welcomed with "great shot of ordnance in all places there about, as well out of the Tower as out of the ships".[37] The following day, the nobles of the realm made their obeisance to Edward at the Tower, and Seymour was announced as Protector.[36] Henry VIII was buried at Windsor on 16 February, in the same tomb as Jane Seymour, as he had wished. Edward VI was crowned at Westminster Abbey four days later on Sunday 20 February, the first coronation in England for almost 40 years.[38] The ceremonies were shortened, because of the "tedious length of the same which should weary and be hurtsome peradventure to the King's majesty, being yet of tender age", and also because the Reformation had rendered some of them inappropriate.[39] On the eve of the coronation, Edward progressed on horseback from the Tower to the Palace of Westminster through thronging crowds and pageants, many based on the pageants for a previous boy king, Henry VI.[40] He laughed at a Spanish tightrope walker who "tumbled and played many pretty toys" outside St Paul's Cathedral.[41] At the coronation service, Cranmer affirmed the royal supremacy and called Edward a second Josiah,[42] urging him to continue the reformation of the Church of England, "the tyranny of the Bishops of Rome banished from your subjects, and images removed".[43] After the service, Edward presided at a banquet in Westminster Hall, where, he recalled in his Chronicle, he dined with his crown on his head.[44]

Edward became ill in January 1553 with a fever and cough that gradually worsened. The imperial ambassador, Scheyfve, reported that "he suffers a good deal when the fever is upon him, especially from a difficulty in drawing his breath, which is due to the compression of the organs on the right side ... I opine that this is a visitation and sign from God".[168] Edward felt well enough in early April to take the air in the park at Westminster and to move to Greenwich, but by the end of the month he had weakened again. By 7 May he was "much amended" and the royal doctors had no doubt of his recovery. A few days later the king was watching the ships on the Thames, sitting at his window.[169] However, he relapsed, and on 11 June Scheyfve, who had an informant in the king's household, reported that "the matter he ejects from his mouth is sometimes coloured a greenish yellow and black, sometimes pink, like the colour of blood".[170] Now his doctors believed he was suffering from "a suppurating tumour" of the lung and admitted that Edward's life was beyond recovery.[171] Soon, his legs became so swollen that he had to lie on his back, and he lost the strength to resist the disease. To his tutor John Cheke, he whispered "I am glad to die".[172] Edward made his final appearance in public on 1 July, when he showed himself at his window in Greenwich Palace, horrifying those who saw him by his "thin and wasted" condition. During the next two days, large crowds arrived hoping to see the king again, but on the 3rd, they were told that the weather was too chilly for him to appear. Edward died at the age of 15 at Greenwich Palace on 6 July 1553. According to John Foxe's legendary account of his death, his last words were: "I am faint; Lord have mercy upon me, and take my spirit".[173] He was buried in Henry VII Lady Chapel at Westminster Abbey on 8 August 1553, with reformed rites performed by Thomas Cranmer. The procession was led by "a grett company of chylderyn in ther surples" and watched by Londoners "wepyng and lamenting"; the funeral chariot, draped in cloth of gold, was topped by an effigy of Edward, with crown, sceptre, and garter.[174] At the same time, Queen Mary attended a mass for his soul in the Tower, where Jane Grey was by then a prisoner. The cause of Edward VI's death is not certain. As with many royal deaths in the 16th century, rumours of poisoning abounded, but no evidence has been found to support these.[175] The Duke of Northumberland, whose unpopularity was underlined by the events that followed Edward's death, was widely believed to have ordered the imagined poisoning.[176] Another theory held that Edward had been poisoned by Catholics seeking to bring Mary to the throne.[177] The surgeon who opened Edward's chest after his death found that "the disease whereof his majesty died was the disease of the lungs".[178] The Venetian ambassador reported that Edward had died of consumption—in other words, tuberculosis—a diagnosis accepted by many historians.[179] Skidmore believes that Edward contracted the tuberculosis after a bout of measles and smallpox in 1552 that suppressed his natural immunity to the disease.[178] Loach suggests instead that his symptoms were typical of acute bronchopneumonia, leading to a "suppurating pulmonary infection" or lung abscess, septicaemia, and kidney failure.[180]