Henry VIII's first marriage had its origins in 1502 when his elder brother, Arthur, died. Their father, Henry VII, then betrothed Arthur's widow, Catherine of Aragon, to the Future king. The betrothal immediately raised questions related to the biblical prohibition (in Leviticus 18 and 20) against marriage to a brother's wife. The couple married in 1509 and after a series of miscarriages, a daughter, Mary, was born in 1516. By the 1520s, Henry still did not have a son to name as heir and he took this as a sure sign of God's anger and made overtures to the Vatican about an annulment. He gave Cardinal Wolsey the task of prosecuting his case; Wolsey began by consulting university experts. From 1527, in addition to his duties as a Cambridge don, Cranmer assisted with the annulment proceedings.

Not much is known about Cranmer's thoughts and experiences during his three decades at Cambridge. Traditionally, he has been portrayed as a humanist whose enthusiasm for biblical scholarship prepared him for the adoption of Lutheran ideas, which were spreading during the 1520s. However, a study of his marginalia reveals an early antipathy to Martin Luther and an admiration for Erasmus. When Cardinal Wolsey, the king's Lord Chancellor, selected several Cambridge scholars, including Edward Lee, Stephen Gardiner and Richard Sampson, to be diplomats throughout Europe, Cranmer was chosen to take a minor role in the English embassy in Spain. Two recently discovered letters written by Cranmer describe an early encounter with the king, Henry VIII of England: upon Cranmer's return from Spain, in June 1527, the king personally interviewed Cranmer for half an hour. Cranmer described the king as "the kindest of princes".

In the summer of 1529, Cranmer stayed with relatives in Waltham Holy Cross to avoid an outbreak of the plague in Cambridge. Two of his Cambridge associates, Stephen Gardiner and Edward Foxe, joined him. The three discussed the annulment issue and Cranmer suggested putting aside the legal case in Rome in favour of a general canvassing of opinions from university Theologians throughout Europe. Henry showed much interest in the idea when Gardiner and Foxe presented him this plan. It is not known whether the king or his new Lord Chancellor, Thomas More, explicitly approved the plan. Eventually it was implemented and Cranmer was requested to join the royal team in Rome to gather opinions from the universities. Edward Foxe coordinated the research effort and the team produced the Collectanea Satis Copiosa ("The Sufficiently Abundant Collections") and The Determinations, historical and theological support for the argument that the king exercised supreme jurisdiction within his realm.

Cranmer's first contact with a Continental reformer was with Simon Grynaeus, a humanist based in Basel, Switzerland, and a follower of the Swiss reformers, Huldrych Zwingli and Johannes Oecolampadius. In the summer of 1531, Grynaeus took an extended visit to England to offer himself as an intermediary between the king and the Continental reformers. He struck up a friendship with Cranmer and after his return to Basel, he wrote about Cranmer to the German reformer Martin Bucer in Strasbourg. Grynaeus' early contacts initiated Cranmer's eventual relationship with the Strasbourg and Swiss reformers.

While Cranmer was following Charles through Italy, he received a royal letter dated 1 October 1532 informing him that he had been appointed the new Archbishop of Canterbury, following the death of archbishop william Warham. Cranmer was ordered to return to England. The appointment had been secured by the family of Anne Boleyn, who was being courted by Henry. When Cranmer's promotion became known in London, it caused great surprise as Cranmer had previously held only minor positions in the Church. Cranmer left Mantua on 19 November and arrived in England at the beginning of January. Henry personally financed the papal bulls necessary for Cranmer's promotion to Canterbury. The bulls were easily acquired because the papal nuncio was under orders from Rome to please the English in an effort to prevent a final breach. The bulls arrived around 26 March 1533 and Cranmer was consecrated as archbishop on 30 March in St Stephen's Chapel. Even while they were waiting for the bulls, Cranmer continued to work on the annulment proceedings, which required greater urgency after Anne announced her pregnancy. Henry and Anne were secretly married on 24 or 25 January 1533 in the presence of a handful of witnesses. Cranmer did not learn of the marriage until a fortnight (14 days) later.

It is difficult to assess how Cranmer's theological views had evolved since his Cambridge days. There is evidence that he continued to support humanism; he renewed Erasmus' pension that had previously been granted by Archbishop Warham. In June 1533, he was confronted with the difficult task of not only disciplining a reformer, but also seeing him burnt at the stake. John Frith was condemned to death for his views on the eucharist: he denied the real presence. Cranmer personally tried to persuade him to change his views without success. Although he rejected Frith's radicalism, by 1534 he clearly signalled that he had broken with Rome and that he had set a new theological course. He supported the cause of reform by gradually replacing the old guard in his ecclesiastical province with men who followed the new thinking such as Hugh Latimer. He intervened in religious disputes, supporting reformers to the disappointment of religious conservatives who desired to maintain the link with Rome.

Cranmer was not immediately accepted by the bishops within his province. When he attempted a canonical visitation, he had to avoid locations where a resident conservative bishop might make an embarrassing personal challenge to his authority. In 1535, Cranmer had difficult encounters with several bishops, John Stokesley, John Longland, and Stephen Gardiner among others. They objected to Cranmer's power and title and argued that the Act of Supremacy did not define his role. This prompted Thomas Cromwell, the king's chief minister, to activate and to take the office of the vicegerent, the deputy supreme head of ecclesiastical affairs. He created another set of institutions that gave a clear structure to the royal supremacy. Hence, the archbishop was eclipsed by Vicegerent Cromwell in regards to the king's spiritual jurisdiction. There is no evidence that Cranmer resented his position as junior partner. Although he was an exceptional scholar, he lacked the political ability to outface even clerical opponents. Those tasks were left to Cromwell.

In the autumn of 1536, the north of England was convulsed in a series of uprisings collectively known as the Pilgrimage of Grace, the most serious opposition to Henry's policies. Cromwell and Cranmer were the primary targets of the protesters' fury. Cromwell and the king worked furiously to quell the rebellion, while Cranmer kept a low profile. After it was clear that Henry's regime was safe, the government took the initiative to remedy the evident inadequacy of the Ten Articles. The outcome after months of debate was The Institution of a Christian Man informally known from the first issue as the Bishops' Book. The book was initially proposed in February 1537 in the first vicegerential synod, ordered by Cromwell, for the whole Church. Cromwell opened the proceedings, but as the synod progressed, Cranmer and Foxe took on the chairmanship and the co-ordination. Foxe did most of the final editing and the book was published in late September.

In 1538, the king and Cromwell arranged with Lutheran princes to have detailed discussions on forming a political and religious alliance. Henry had been seeking a new embassy from the Schmalkaldic League since summer 1537. The Lutherans were delighted by this and they sent a joint delegation from various German cities, including a colleague of Martin Luther, Friedrich Myconius. The delegates arrived in England on 27 May 1538. After initial meetings with the king, Cromwell, and Cranmer, discussions on theological differences were transferred to Lambeth Palace under Cranmer's chairmanship. Progress on an agreement was slow partly due to Cromwell being too busy to help expedite the proceedings and partly due to the negotiating team on the English side, which was evenly balanced between conservatives and reformers. The talks dragged on through the summer with the Germans becoming weary despite the Archbishop's strenuous efforts. The negotiations, however, were fatally neutralised by an appointee of the king. Cranmer's colleague, Edward Foxe, who sat on Henry's Privy Council, had died earlier in the year. The king chose as his replacement Cranmer's conservative rival, Cuthbert Tunstall, who was told to stay near Henry to give advice. On 5 August, when the German delegates sent a letter to the king regarding three items that particularly worried them (compulsory clerical celibacy, the withholding of the chalice from the laity, and the maintenance of private masses for the dead), Tunstall was able to intervene for the king and to influence the decision. The result was a thorough dismissal by the king of many of the Germans' chief concerns. Although Cranmer begged the Germans to continue with the negotiations using the argument "to consider the many thousands of souls in England" at stake, they left on 1 October having made no substantial achievements.

Cranmer's family had been exiled to the Continent in 1539. It is not known exactly when they returned to England, but it was soon after the accession of Edward VI in 1547 that Cranmer publicly acknowledged their existence. Not much is known about the early years of the children. His daughter, Margaret, was likely born in the 1530s and his son, Thomas, came later, probably during the reign of Edward. Sometime around Mary's accession, Cranmer's wife, Margarete, escaped to Germany, while his son was entrusted to his brother, Edmund Cranmer, who took him too to the Continent. Margarete Cranmer eventually married Cranmer's favourite publisher, Edward Whitchurch. The couple returned to England after Mary's reign and settled in Surrey. Whitchurch also negotiated for the marriage of Margaret to Thomas Norton. Whitchurch died in 1562 and Margarete married for the third time to Bartholomew Scott. She died in the 1570s. Both of Cranmer's children died without issue and his line became extinct.

The setback for the reformers was short-lived. By September, Henry was displeased with the results of the Act and its promulgators; the ever-loyal Cranmer and Cromwell were back in favour. The king asked his archbishop to write a new preface for the Great Bible, an English translation of the Bible that was first published in April 1539 under the direction of Cromwell. The preface was in the form of a sermon addressed to readers. As for Cromwell, he was delighted that his plan of a royal marriage between Henry and Anne of Cleves, the sister of a German Prince was accepted by the king. In Cromwell's view, the marriage could potentially bring back contacts with the Schmalkaldic League. Henry was dismayed with Anne when they first met on 1 January 1540 but married her reluctantly on 6 January in a ceremony officiated by Cranmer. However, the marriage ended in disaster as Henry decided shortly thereafter that he would request a royal divorce. This resulted in Henry being placed in an embarrassing position and Cromwell suffered the consequences. His old enemies, including the Duke of Norfolk, took advantage of the weakened Cromwell and he was arrested on 10 June. He immediately lost the support of all his friends, including Cranmer. However, as Cranmer had done for Anne Boleyn, he wrote a letter to the king defending the past work of Cromwell. Henry's marriage to Anne of Cleves was quickly annulled on 9 July by the vice-gerential synod, now led by Cranmer and Gardiner.

Following the annulment, Cromwell was executed on 28 July. Cranmer now found himself in a politically prominent position, with no-one else to shoulder the burden. Throughout the rest of Henry's reign, he clung to Henry's authority. The king had total trust in him and in return, Cranmer could not conceal anything from the king. At the end of June 1541, Henry with his new wife, Catherine Howard, left for his first visit to the north of England. Cranmer was left in London as a member of a council taking care of matters for the king in his absence. His colleagues were Lord Chancellor Thomas Audley and Edward Seymour, Earl of Hertford. This was Cranmer's first major piece of responsibility outside the Church. In October, while the king and queen were away, a reformer named John Lascelles revealed to Cranmer that Catherine engaged in extramarital affairs. Cranmer gave the information to Audley and Seymour and they decided to wait until Henry's return. Afraid of angering the king, Audley and Seymour suggested that Cranmer inform Henry. Cranmer slipped a message to Henry during mass on All Saints Day. An investigation revealed the truth of the marital indiscretions and Catherine was executed in February 1542.

For five months, Henry took no action on the accusations against his archbishop. The conspiracy was finally revealed to Cranmer by the king himself. According to Cranmer's secretary, Ralph Morice, sometime in September 1543 the king showed Cranmer a paper summarising the accusations against him. An investigation was to be mounted and Cranmer was appointed chief investigator. Surprise raids were carried out, evidence gathered, and ringleaders identified. Typically, Cranmer put the clergymen involved in the conspiracy through immediate humiliation, but he eventually forgave them and continued to use their services. To show his trust in Cranmer, Henry gave Cranmer his personal ring. When the Privy Council arrested Cranmer at the end of November, the nobles were stymied by the symbol of the king's trust in him. Cranmer's victory ended with two second-rank Leaders imprisoned and Germain Gardiner executed.

With the atmosphere in Cranmer's favour, he pursued quiet efforts to reform the Church, particularly the liturgy. On 27 May 1544 the first officially authorised vernacular Service was published, the processional Service of intercession known as the Exhortation and Litany. It survives today with minor modifications in the Book of Common Prayer. The traditional litany uses invocations to saints, but Cranmer thoroughly reformed this aspect by providing no opportunity in the text for such veneration. Additional reformers were elected to the House of Commons and new legislation was introduced to curb the effects of the Act of the Six Articles and the Act for the Advancement of True Religion.

Cranmer's eucharistic views, which had already moved away from official Catholic doctrine, received another push from Continental reformers. Cranmer had been in contact with Martin Bucer since the time when initial contacts were made with the Schmalkaldic League. However, Cranmer and Bucer's relationship became ever closer due to Charles V's victory over the League at Mühlberg, which left England as the sole major nation that gave sanctuary to persecuted reformers. Cranmer wrote a letter to Bucer (now lost) with questions on eucharistic theology. In Bucer's reply dated 28 November 1547, he denied the corporeal real presence and condemned transubstantiation and the adoration of the elements. The letter was delivered to Cranmer by two Italian reformed Theologians, Peter Martyr and Bernardino Ochino who were invited to take refuge in England. Martyr also brought with him an epistle written allegedly by John Chrysostom (now regarded as a forgery), Ad Caesarium Monachum, which appeared to provide patristic support against the corporeal real presence. These documents were to influence Cranmer's thoughts on the eucharist.

As the use of English in worship services spread, the need for a complete uniform liturgy for the Church became evident. Initial meetings to start what would eventually become the Book of Common Prayer were held in the former abbey of Chertsey and in Windsor Castle in September 1548. The list of participants can only be partially reconstructed, but it is known that the members were balanced between conservatives and reformers. These meetings were followed by a debate on the Eucharist in the House of Lords which took place between 14 and 19 December. Cranmer publicly revealed in this debate that he had abandoned the doctrine of the corporeal real presence and believed that the Eucharistic presence was only spiritual. Parliament backed the publication of the Prayer Book after Christmas by passing the Act of Uniformity 1549; it then legalized clerical marriage.

The origins of the Statement that eventually became the Forty-Two Articles are equally obscure. As early as December 1549, the archbishop was demanding from his bishops subscription to certain doctrinal articles. In 1551 Cranmer presented a version of a statement to the bishops, but its status remained ambiguous. Cranmer did not devote much effort into developing the articles, most likely due to work on the canon law revision. He became more interested once the hope for an ecumenical council began to fade. By September 1552, draft versions of the articles were being worked on by Cranmer and John Cheke, his scholarly friend who was commissioned to translate them into Latin. When the Forty-Two Articles were finally published in May 1553, the title-page declared that the articles were agreed upon by the Convocation and were published by the authority of the king. This was not in fact the case and the mistake was likely caused by miscommunications between the archbishop and the Privy Council. Cranmer complained about this to the council, but the authorities responded by noting that the articles were developed during the time of the Convocation—hence evading a direct answer. The council gave Cranmer the unfortunate task of requiring subscription to the articles from the bishops, many of whom opposed them and pointed out the Anomaly of the title-page. It was while Cranmer was carrying out this duty that events unfolded that would render the subscriptions futile.

Although Bucer assisted in the development of the English Reformation, he was still quite concerned about the speed of its progress. Both Bucer and Fagius had noticed that the 1549 Prayer Book was not a remarkable step forward, although Cranmer assured Bucer that it was only a first step and that its initial form was only temporary. However, by the winter 1550, Bucer was becoming disillusioned. Cranmer, however, made sure that he did not feel alienated and kept in close touch with him. This attention paid off during the vestments controversy. This incident was initiated by John Hooper, a follower of Heinrich Bullinger who had recently returned from Zürich. Hooper was unhappy with Cranmer's Prayer Book and Ordinal and he particularly objected to the use of ceremonies and vestments. When the Privy Council selected him to be the Bishop of Gloucester on 15 May 1550, he laid down conditions that he would not wear the required vestments. He found an ally among the Continental reformers in Jan Łaski who had become a leader of the Stranger church in London, a designated place of worship for Continental Protestant refugees. His church's forms and practices had taken reforms much further than Cranmer would have liked. However, Bucer and Peter Martyr, while they sympathised with Hooper's position, supported Cranmer's arguments of timing and authority. Cranmer and Ridley stood their ground. This led to Hooper's imprisonment and he eventually gave in. He was consecrated on 8 March 1551 according to the Ordinal and he preached before the king in his episcopal garments. Cranmer's vision of reform through careful steps under the authority of the government was maintained.

The original Roman canon law that defined governance within the Church clearly needed revision following Henry's break with Rome. Several revision attempts were made throughout Henry's reign, but these initial projects were shelved as the speed of reform outpaced the time required to work on a revision. As the reformation stabilised, Cranmer formed a committee in December 1551 to restart the work. He recruited Peter Martyr to the committee and he also asked Łaski and Hooper to participate, demonstrating his usual ability to forgive past actions. Cranmer and Martyr realised that a successful enactment of a reformed ecclesiastical law-code in England would have international significance. Cranmer planned to draw together all the reformed churches of Europe under England's leadership to counter the Council of Trent, the Roman Catholic Church's response to the Protestant Reformation. In March 1552, Cranmer invited the foremost Continental reformers, Bullinger, John Calvin, and Melanchthon to come to England and to participate in an ecumenical council. The response was disappointing: Melanchthon did not respond, Bullinger stated that neither of them could leave Germany as it was riven by war between the Emperor and the Lutheran princes, and while Calvin showed some enthusiasm, he said he was unable to come. Cranmer acknowledged Calvin and replied stating, "Meanwhile we will reform the English Church to the utmost of our ability and give our labour that both its doctrines and laws will be improved after the model of holy scripture." One partial manuscript of the project survived that was annotated with corrections and comments by Cranmer and Martyr. When the final version was presented to Parliament, the breach between Cranmer and Dudley was complete and the regent effectively killed the canon law bill in the House of Lords.

When Elizabeth I came to power she restored the Church of England's independence from Rome under the Elizabethan Religious Settlement. The church that she re-established represented, in effect, a snapshot of the Edwardian Church from September 1552. Thus the Elizabethan Prayer Book was basically Cranmer's 1552 edition but without the "Black Rubric". In the Convocation of 1563 the Forty-Two Articles which were never adopted by the Church were altered in the area of eucharistic doctrine to form the Thirty-Nine Articles. Most of the exiles returned to England and resumed their careers in the Church. To some like Edmund Grindal, an Archbishop of Canterbury during Elizabeth's reign, Cranmer provided a shining Example whose work should be upheld and extended.

On 13 November 1553 Cranmer and four others were brought to trial for treason, found guilty, and condemned to death. Several enemies testified that Cranmer had encouraged heresy and had written heretical works. Throughout February 1554 Jane Grey and other rebels were executed. It was now time to deal with the religious Leaders of the reformation and so on 8 March 1554 the Privy Council ordered Cranmer, Ridley, and Latimer to be transferred to Bocardo prison in Oxford to await a second trial for heresy. During this time Cranmer was able to smuggle out a letter to Martyr who had fled to Strasbourg, the last surviving document written in his own hand. He stated that the desperate situation of the church was proof that it will eventually be delivered and wrote, "I pray that God may grant that we may endure to the end!" Cranmer remained isolated in Bocardo prison for seventeen months before the trial started on 12 September 1555. Although it took place in England, the trial was under papal jurisdiction and the final verdict would come from Rome. Under interrogation, Cranmer admitted to every fact that was placed before him, but he denied any treachery, disobedience, or heresy. The trial of Latimer and Ridley started shortly after Cranmer's but their verdicts came almost immediately and they were burnt at the stake on 16 October. Cranmer was taken to a tower to watch the proceedings. On 4 December, Rome decided Cranmer's fate by depriving him of the archbishopric and giving permission to the secular authorities to carry out their sentence.

In his final days Cranmer's circumstances changed, which led to several recantations. On 11 December, Cranmer was taken out of Bocardo and placed in the house of the Dean of Christ Church. This new environment was very different from that of his two years in prison. He was in an academic community and treated as a guest. Approached by a Dominican friar, Juan de Villagarcia, he debated the issues of papal supremacy and purgatory. In his first four recantations, produced between the end of January and mid-February, Cranmer submitted himself to the authority of the king and queen and recognised the pope as head of the church. On 14 February 1556, he was degraded from holy orders and returned to Bocardo. He had conceded very little and Edmund Bonner was not satisfied with these admissions. On 24 February a writ was issued to the mayor of Oxford and the date of Cranmer's execution was set for 7 March. Two days after the writ was issued, a fifth statement, the first which could be called a true recantation was issued. Cranmer repudiated all Lutheran and Zwinglian theology, fully accepted Catholic theology including papal supremacy and transubstantiation, and stated that there was no salvation outside the Catholic Church. He announced his joy of returning to the Catholic faith, asked for and received sacramental absolution, and participated in the mass. Cranmer's burning was postponed and under normal practice of canon law, he should have been absolved. Mary, however, decided that no further postponement was possible. His last recantation was issued on 18 March. It was a sign of a broken man, a sweeping confession of sin. Despite the stipulation in canon law that recanting heretics be reprieved, Mary was determined to make an Example of Cranmer, arguing that "his iniquity and obstinacy was so great against God and your Grace that your clemency and mercy could have no place with him", and pressed ahead with his execution.

The Marian government produced a pamphlet with all six recantations plus the text of the speech Cranmer was to have made in the University Church. His subsequent withdrawal of his recantations was not mentioned, though what actually happened soon became Common knowledge, undermining the effectiveness of Marian propaganda. Similarly, the Protestant party had difficulty in making use of the event, given Cranmer's recantations. The exiles' propaganda concentrated on publishing various specimens of his writings. Eventually John Foxe put Cranmer's story to effective use in 1559, and it features prominently in his Acts and Monuments when it was first printed in 1563.