Edward VI was only nine years old when he became king in 1547. His uncle, Edward Seymour, 1st Duke of Somerset tampered with Henry VIII's will and obtained letters patent giving him much of the power of a monarch by March 1547. He took the title of Protector. Somerset, disliked by the Regency Council for being autocratic, was removed from power by John Dudley, who is known as Lord President Northumberland. Northumberland proceeded to adopt the power for himself, but he was more conciliatory and the Council accepted him. During Edward's reign England changed from being a Catholic nation to a Protestant one, in schism from Rome. Edward showed great promise but fell violently ill of tuberculosis in 1553 and died that August, two months before his 16th birthday.

Northumberland made plans to place Lady Jane Grey on the throne and marry her to his son, so that he could remain the power behind the throne. His plot failed in a matter of days, Jane Grey was beheaded, and Mary I (1516–1558) took the throne amidst popular demonstration in her favour in London, which contemporaries described as the largest show of affection for a Tudor monarch. Mary had never been expected to hold the throne, at least not since Edward was born. She was a devoted Catholic who believed that she could reverse the Reformation.

Returning England to Catholicism led to the burnings of 274 Protestants, which are recorded especially in John Foxe's Book of Martyrs. Mary then married her cousin Philip, son of Emperor Charles V, and King of Spain when Charles abdicated in 1556. The union was difficult because Mary was already in her late 30s and Philip was a Catholic and a foreigner, and so not very welcome in England. This wedding also provoked hostility from France, already at war with Spain and now fearing being encircled by the Habsburgs. Calais, the last English outpost on the Continent, was then taken by France. Mary's death in November 1558 was greeted with huge celebrations in the streets of London.