Cecil was born in Bourne, Lincolnshire, in 1521, the son of Richard Cecil, owner of the Burghley estate (near Stamford, Lincolnshire), and his wife, Jane Heckington. Pedigrees, elaborated by Cecil himself with the help of William Camden the antiquary, associated him with the Welsh Cecils or Sitsylts of Allt - Yr - Ynys, Walterstone, on the border of Herefordshire and Monmouthshire, and traced his descent from an Owen of the time of King Harold and a Sitsyllt of the reign of William Rufus. Sitsylt is the original Welsh spelling of the anglicised Cecil. There is now no doubt that the family was from the Welsh Marches and Lord Burghley himself acknowledged this in his family pedigree painted at Theobalds. The family had connections with Dore Abbey. However, the move to Stamford provides information concerning the Lord Treasurer's grandfather, David; he, according to Burghley's enemies, kept the best inn in Stamford. David somehow secured the favour of the first Tudor Henry VII, to whom he seems to have been Yeoman of the Guard. He was Sergeant - of - Arms to Henry VIII in 1526, Sheriff of Northamptonshire in 1532, and a Justice of the Peace for Rutland. His eldest son, Richard, Yeoman of the Wardrobe (d. 1554), married Jane, daughter of William Heckington of Bourne, and was father of three daughters and the future Lord Burghley.

William, the only son, was put to school first at The King's School, Grantham and then at Stamford School, which he later saved and endowed. In May 1535, at the age of fourteen, he went up to St John's College, Cambridge, where he was brought into contact with the foremost educators of the time, Roger Ascham and John Cheke, and acquired an unusual knowledge of Greek. He also acquired the affections of Cheke's sister, Mary, and was in 1541 removed by his father to Gray's Inn, without, after six years' residence at Cambridge, having taken a degree. The precaution proved useless and four months later Cecil committed one of the rare rash acts of his life in marrying Mary Cheke. The only child of this marriage, Thomas, the future Earl of Exeter, was born in May 1542, and in February 1543 Cecil's first wife died. Three years later, on 21 December 1546 he married Mildred Cooke, who was ranked by Ascham with Lady Jane Grey as one of the two most learned ladies in the kingdom, and whose sister, Anne, became the wife of Sir Nicholas (and the mother of Sir Francis) Bacon.

William Cecil's early career was spent in the service of the Duke of Somerset (a brother of the late queen, Jane Seymour), who was Lord Protector during the early years of the reign of his nephew, the young Edward VI. Cecil accompanied Somerset on his Pinkie campaign of 1547 (part of the "Rough Wooing"), being one of the two Judges of the Marshalsea. The other was William Patten, who states that both he and Cecil began to write independent accounts of the campaign, and that Cecil generously contributed his notes for Patten's narrative of the "Expedition into Scotland".

Cecil, according to his autobiographical notes, sat in Parliament in 1543; but his name does not occur in the imperfect parliamentary returns until 1547, when he was elected for the family borough of Stamford.

In 1548, he is described as the Protector's Master of Requests, which apparently means that he was clerk or registrar of the court of requests which the Protector, possibly at Hugh Latimer's instigation, illegally set up in Somerset House to hear poor men's complaints. He also seems to have acted as private secretary to the Protector, and was in some danger at the time of the Protector's fall in October 1549. The lords opposed to Somerset ordered his detention on 10 October, and in November he was in the Tower of London.

Cecil ingratiated himself with Warwick, and after less than three months he was out of the Tower. On 5 September 1550 Cecil was sworn in as one of King Edward's two Secretaries of State. In April 1551, Cecil became Chancellor of the Order of the Garter. But service under Warwick (by now the Duke of Northumberland) carried some risk, and decades later in his diary, Cecil recorded his release in the phrase "ex misero aulico factus liber et mei juris" ("I was freed from this miserable court").

To protect the Protestant government from the accession of a Catholic queen, Northumberland forced King Edward's lawyers to create an instrument setting aside the Third Succession Act on 15 June 1553. (The document, which Edward titled "My Devise for the Succession", barred both Elizabeth and Mary, the remaining children of Henry VIII, from the throne, in favour of Lady Jane Grey.) Cecil resisted for a while, in a letter to his wife, he wrote: "Seeing great perils threatened upon us by the likeness of the time, I do make choice to avoid the perils of God's displeasure." But at Edward's royal command he signed it. He signed not only the devise, but also the bond among the conspirators and the letters from the council to Mary Tudor of 9 June 1553.

Years afterwards, he pretended that he had only signed the devise as a witness, but in his apology to Queen Mary I, he did not venture to allege so flimsy an excuse; he preferred to lay stress on the extent to which he succeeded in shifting the responsibility on to the shoulders of his brother - in - law, Sir John Cheke, and other friends, and on his intrigues to frustrate the Queen to whom he had sworn allegiance.

There is no doubt that Cecil saw which way the wind was blowing, and disliked Northumberland's scheme; but he had not the courage to resist the duke to his face. As soon, however, as the duke had set out to meet Mary, Cecil became the most active intriguer against him, and to these efforts, of which he laid a full account before Queen Mary, he mainly owed his immunity. He had, moreover, had no part in the divorce of Catherine of Aragon or in the humiliation of Mary during Henry's reign, and he made no scruple about conforming to the Catholic reaction. He went to Mass, confessed, and in no particular official capacity went to meet Cardinal Pole on his return to England in December 1554, again accompanying him to Calais in May 1555.

It was rumoured in December 1554 that Cecil would succeed Sir William Petre as Secretary of State, an office which, with his chancellorship of the Garter, he had lost on Mary's accession to the throne. Probably the Queen had more to do with this rumour than Cecil, though he is said to have opposed, in the parliament of 1555 (in which he represented Lincolnshire), a bill for the confiscation of the estates of the Protestant refugees. But the story, even as told by his biographer, does not represent Cecil's conduct as having been very courageous; and it is more revealing that he found no seat in the parliament of 1558, for which Mary had directed the return of "discreet and good Catholic members".

The Duke of Northumberland had employed Cecil in the administration of the lands of Princess Elizabeth. Before Mary died he was a member of the "old flock of Hatfield", and from the first, the new Queen relied on Cecil. She appointed him Secretary of State. His tight control over the finances of the Crown, leadership of the Privy Council, and the creation of a highly capable intelligence service under the direction of Francis Walsingham made him the most important minister for the majority of Elizabeth's reign.

Though a Protestant, Cecil was not a religious purist; he aided the Huguenots and the Dutch just enough to keep them going in the struggles which warded danger from England's shores. But Cecil never developed that passionate aversion from decided measures which became a second nature to Elizabeth. His intervention in Scotland in 1559 – 1560 showed that he could strike hard when necessary; and his action over the execution of Mary, Queen of Scots, proved that he was willing to take on responsibilities from which the Queen shrank. The American international relations theorist Hans Morgenthau claimed Burghley accepted a pension (a bribe) from Spain, although Burghley's biographer Conyers Read has claimed that there is no evidence for this.

Generally he was in favour of more decided intervention on behalf of continental Protestants than Elizabeth would have liked, but it is not always easy to ascertain the advice he gave. He left endless memoranda lucidly (nevertheless sometimes bordering on the ridiculous) setting forth the pros and cons of every course of action; but there are few indications of the line which he actually recommended when it came to a decision. How far he was personally responsible for the Anglican Settlement, the Poor Laws, and the foreign policy of the reign, remains to a large extent a matter of conjecture. However, it is most likely that Cecil's views carried the day in the politics of Elizabethan England.

His share in the Religious Settlement of 1559 was considerable, and it coincided fairly with his own Anglican religious views. Like the mass of the nation, he grew more Protestant as time wore on; he was happier to persecute Catholics than Puritans; and he had no love for ecclesiastical jurisdiction. He warmly remonstrated with John Whitgift, the Anglican Archbishop of Canterbury, over his persecuting Articles of 1583. The finest encomium was passed on him by the queen herself, when she said, "This judgment I have of you, that you will not be corrupted with any manner of gifts, and that you will be faithful to the state."

He represented Lincolnshire in the Parliament of 1559, and Northamptonshire in that of 1563, and he took an active part in the proceedings of the House of Commons until his elevation to the peerage; but there seems no good evidence for the story that he was proposed as Speaker in 1563. In January 1561, he was given the lucrative office of Master of the Court of Wards and Liveries in succession to Sir Thomas Parry, and he did something to reform that instrument of tyranny and abuse. In February 1559, he was elected Chancellor of Cambridge University in succession to Cardinal Pole; he was created M.A. of that university on the occasion of Elizabeth's visit in 1564, and M.A. of Oxford on a similar occasion in 1566. He was the first Chancellor of Trinity College, Dublin, between 1592 and 1598.

On 25 February 1571, in anticipation of the impending marriage of his daughter Anne Cecil (b. 1556) to Edward de Vere, 17th Earl of Oxford, Queen Elizabeth elevated him as Baron Burghley. The fact that Burghley continued to act as Secretary of State after his elevation illustrates the growing importance of that office, which under his son became a secretary of the ship of state. In 1572, however, Lord Winchester, who had been Lord High Treasurer under Edward, Mary and Elizabeth, died. His vacant post was offered to Robert Dudley, 1st Earl of Leicester, who declined it and proposed Burghley, stating that the latter was the more suitable candidate because of his greater "learning and knowledge". The new Lord Treasurer's hold over the queen strengthened with the years. He collapsed (possibly from a stroke or heart attack) in 1592. Before he died, Robert, his only surviving son by his second wife, was ready to step into his shoes as the Queen's principal adviser. Having survived all his children except Robert and Thomas, Burghley died at his London residence on 4 August 1598, and was buried in St Martin's Church, Stamford.

His younger son, Sir Robert Cecil (later created Baron Cecil, Viscount Cranborne and finally Earl of Salisbury), inherited his political mantle, taking on the role of chief minister and arranging a smooth transfer of power to the Stuart administration under King James I. His elder son, Sir Thomas Cecil, who inherited the Barony of Burghley on his death, was later created Earl of Exeter.

In contrast to his public unscrupulousness, Burghley's private life seems to have been upright; he was a faithful husband, a careful father and a dutiful master. A book lover and antiquarian, he made a special hobby of heraldry and genealogy. It was the conscious and unconscious aim of the age to reconstruct a new landed aristocracy on the ruins of the old, Catholic order. As such, Burghley was a great builder, planter and patron. All the arts of architecture and horticulture were lavished on Burghley House and Theobalds (which his son, Robert, was to exchange with James I for Hatfield House). As the Marquess of Winchester (Burghley's predecessor as Lord High Treasurer) had said of himself, Burghley was "sprung from the willow rather than the oak". The interests of the State were his supreme consideration and to that end he felt no hesitation in sacrificing his conscience. He frankly disbelieved in toleration: "That State... could never be in safety where there was a toleration of two religions. For there is no enmity so great as that for religion; and therefore they that differ in the service of their God can never agree in the service of their country." With a maxim such as this, it was easy for him to maintain that Elizabeth's — and his — brutal measures were political and not religious. To say that he was Machiavellian is pointless, for every statesman is so, more or less; especially in the 16th century men preferred efficiency over principle. On the other hand, Burghley may have felt that principles are valueless without law and order; and that his craft and subtlety prepared a security in which principles might find some scope.

Burghley's descendants include the Marquesses of Exeter, descended from his elder son Thomas; and the Marquesses of Salisbury, descended from his younger son Robert. One of the latter branch, Robert Cecil, 3rd Marquess of Salisbury (1830 – 1903), served three times as Prime Minister under Queen Victoria and Edward VII.

The most prolonged of Cecil's surviving personal correspondences is with an Irish judge, Nicholas White, lasting from 1566 until 1590; it is contained in the State Papers Ireland 63 and Lansdowne MS 102, but receives hardly a mention in the literature on Cecil. White had been a tutor to Cecil's children during his student days in London, and the correspondence suggests that he was held in lasting affection by the family. In the end, White fell into a Dublin controversy over the confessions of an intriguing priest, which threatened the authority of the Queen's deputised government in Ireland; out of caution Cecil withdrew his longstanding protection, and the judge was imprisoned in London and died soon after. White's most remarked upon service for Cecil is his report on his visit with Mary, Queen of Scots, in 1569, during the early years of her imprisonment by Queen Elizabeth. He may have published an English translation of the Argonautica in the 1560s, but no copy has survived.

As Master of the Court of Wards, Burghley supervised the raising and education of the sons of wealthy aristocrats who had died before their sons had achieved maturity. These included Edward de Vere, 17th Earl of Oxford, Henry Wriothesley, 3rd Earl of Southampton, and Roger Manners, 5th Earl of Rutland. He is widely credited with reforming an institution notorious for its corruption, but the extent of his reforms has been disputed by some scholars, including Joel Hurstfeld.

In his capacity as Principal Secretary, Cecil understood the power of the printed word to affect public opinion. He was active in shaping policy regarding publication and employed translators to make continental works available in English which he identified as useful to supporting the Elizabethan Settlement. His utilitarian view of literature, it has long been supposed by many Elizabethan scholars is parodied in the character of Polonius in Hamlet.

William Cecil has been a character in many works of fiction and documentary essay concerned with Elizabeth I's reign. The most recent, and perhaps best known depiction is by Lord Richard Attenborough in the film Elizabeth. He was also a prominent supporting character in the 1937 film Fire Over England, starring Laurence Olivier, Vivien Leigh, and Flora Robson. Burghley (spelled Burleigh in the film) was played by Morton Selten. He also appears in the television miniseries Elizabeth I with Helen Mirren, in which he is played by Ian McDiarmid. He was also portrayed by Ronald Hines in the 1971 TV series Elizabeth R.

Cecil is also one of 12 main characters, Cecil himself portrayed by David Thewlis, in Roland Emmerich's Anonymous, which supports the idea that the works of William Shakespeare were written by Edward de Vere. His part in this theory largely revolves around his being father - in - law to de Vere, and possibly the model for the character Polonius in Hamlet. The film began filming in April 2010 and has yet to be released.

Cecil appears as a character in the novel I, Elizabeth by Rosalind Miles.

The line "History teaches: never trust a Cecil!" was quoted, inter alia, in regards Lord Cranborne, a contemporary member of the Cecil family who was dismissed from his Conservative Party office in the House of Lords for conducting unauthorised negotiations with the Labour government.