Sir Francis Windebank, the secretary of state, was the only son of Sir Thomas Windebank and his wife, Frances, younger daughter of Sir Edward Dymoke of Scrivelsby in Lincolnshire. He was baptised at St. Martin's-in-the-Fields, Westminster on 21st August 1582 and, on 18th May 1599, matriculated at St. John's College, Oxford. He graduated as a BA on 26th January 1602 and, in the same year, was entered as a student in the Middle Temple. While at St. John's, Windebank came much into contact with Laud, who exercised great influence upon his views and subsequent career. On 21st February 1605, his father procured for him a grant of a clerkship of the signet, in reversion after Levinus Munck and Francis Gage, who themselves held only a reversionary interest in the office; and this somewhat distant prospect was no bar to a few years' sojourn on the Continent.

In the Autumn of 1605, Windebank was in Paris, which he proposed to leave on 29th January 1606 "to avoid the profligate English". He spent the Summer in Germany and the following Winter in Italy. He was at Lucca in July 1607 and at Piacenza in the October, returning to England in February 1608 upon hearing of the death of his father the previous October. Thenceforth, his chief residence, when not in London, was Haines Hill in St. Nicholas Hurst (Berkshire). Though the clerkship of the signet did not fall to him for some years, he was almost at once employed in that office. In 1629, he spoke of having served "nigh three apprenticeships" (probably nearly twenty-one years) in the clerkship and having passed through "the active and strict times of Lord Salisbury without check"; and he first got access to the King in 1611. He was placed on the commission of the peace for Berkshire and became clerk of the signet before 1624. He also served, on various other commissions, in one of which George Wither was a colleague (12th February) and was able to befriend John Florio and William Laud, who afterwards spoke of Windebank's "great love and care" during his "great extremity", probably in 1614.

Windebank's political importance had, however, been very slight and the court was considerably surprised when, on 12th June 1632, Sir John Coke informed him that the King had "taken notice of his worth and long service" and selected him as Coke's colleague in the secretaryship in succession to Dudley Carleton, Lord Dorchester. He was sworn in "in the Inner Star Chamber", took his seat at the council on the 15th, and was knighted on the 18th. Sir Thomas Roe, himself a disappointed candidate, wrote, "There is a new secretary brought out of the dark." During this period, Windebank was several times visited at Haines Hill by Archbishop Laud, who preached in the parish church there. He owed his appointment partly to Laud's friendship, but more to the influence of Richard Weston, 1st Earl of Portland, and Francis, Lord Cottington, with whose Spanish sympathies and Roman Catholic tendencies, he was in partial if not in full accord. The three formed an inner ring in the council, by whose advice King Charles was mainly guided till 1640, and with whose help he frequently carried on negotiations unknown and in opposition to the rest of the council. Windebank was one of those of whom Fontenay said in 1634, "L'interest les fait espagnolz, tirans plusieurs notables avantages du commerce et des passeports que le Cte d'Olivares accorde aux marchands qui negotient pour eux". In 1633, he, Portland and Cottington were appointed to negotiate in secret with the Spanish Ambassador, Necolalde, and, in March 1635, with Richelieu's envoy, the Marquis of Seneterre. On Portland's death, in that month, he was one of the commissioners to whose hands the treasury was entrusted, and his conduct in this office led to a breach of his long standing friendship with Laud. The cause was Windebank's consistent support of Cottington over the soap monopoly and his opposition to the Archbishop's endeavours to check the peculation and corruption rampant in high quarters.

Windebank's Roman Catholic tendencies found vent in his negotiations with the Papal Agent, Gregorio Panzani, with whom he was appointed, by King Charles in December 1634, to discuss the possibility of a union between the Anglican and Roman Churches. "Morally and intellectually timid, the secretary was thoroughly alarmed at the progress of Puritanism and looked anxiously about for a shelter against the storm, of which he could avail himself without an absolute surrender of all the ideas which he had imbibed in his childhood and youth. By the side of Portland and Cottington, he shows to advantage. If he was a weak man, he was not without a certain honesty of purpose; and if he missed the way in his searchings after truth, it was least truth that he sought, and not pelf in this world and exemption from punishment in the other". Anxious for the reunion of the churches, he thought it possible, were it not for the Jesuits and Puritans, and suggested that the latter might be got rid of by sending them to the wars in Flanders. He proposed the despatch of a Papal Agent to reside with Queen Henrietta Maria, pointed out to Charles the advantage of having someone to excommunicate unruly subjects and referred to the sacrilege committed by "that pig of a Henry VIII". Later on, in August 1639, he talked to Rossetti, Panzani's successor, "like a zealous catholic", and offered to give him any information of which he stood in need.

Meanwhile, in 1636, Juxon vainly endeavoured to effect a reconciliation between Laud and Windebank and, in July of the same year, the secretary was in temporary disgrace. He was confined to his house, in August, for issuing an order for the conveyance of Spanish money to pay the Spanish army in the Netherlands, but was soon at liberty. In 1637, Charles sent him to the Spanish Ambassador, Onate, to propose one more secret and abortive treaty for the settlement of the Palatinate difficulty and, in the same year, he was engaged in an equally ineffectual attempt to induce Dutch fishermen to take out English licenses to fish in the Narrow Seas. In July 1638, he was one of the committee of the council consulted by Charles with regard to Scotland and, like Arundel and Cottington, he voted for instant war. In May 1639, Windebank was directed, by the King, to spread exaggerated reports as to the number of men at his disposal and, in the June, supported a scheme for compelling the City of London to contribute towards their equipment and maintenance. On 9th March 1640, he was returned to the Short Parliament, as member for Oxford University, and, on 16th April, he read to the house the Scots' letter to Louis XIII. In May, he conveyed a letter from the Queen to Rossetti, asking him to write to Rome for help in both money and men; and, even in June, he saw no difficulty in collecting an army to fight the Scots. His unpopularity was so great that, in the elections to the Long Parliament, even Oxford University preferred Sir Thomas Roe and John Selden, and Windebank was obliged to find a seat for Corfe Castle, for which he was returned on 22nd October. He did not retain it long; for, on 1st December, Glynne reported to the House that Windebank had signed numerous letters in favour of priests and Jesuits, and Hyde declared that "it was not in the wit of man to save Windebank". The house drew up ten articles and sent for Windebank to answer them. The messengers were told that he was ill in bed and, that night he fled with his nephew and secretary, Robert Reade, to Queenborough in Kent, whence he made his way in an open shallop to Calais.

Windebank's flight was the subject of some contemporary satire. In the 'Stage-player's Complaint,' Quick refers to "the times when my tongue have ranne as fast upon the scaene as a Windebankes pen over the ocean"; and in a print by Glover to illustrate 'Four fugitives meeting, or a Discourse amongst my lord Finch, Sir Francis Windebanke, Sir John Sucklin and Doctor Roane', Windebank is represented with a pen behind his ear. He was coupled with Laud in popular hatred and, in a ballad against the pair, is described as "the subtle whirly Windebank".

From Calais, Windebank wrote an eloquent appeal for compassion to Christopher, 1st Lord Hatton. He defended himself from the charge of having been bribed by the Romanists to introduce Popery into England, declared that he held the English Church to be "not only a true and orthodox church, but the most pure and neere the primitive of any in the Christian World," and that he had not added one foot of land to the five hundred pounds' worth left him by his father - a poor return for their eighty years spent in the service of the state. He wrote in a similar strain to Robert Devereux, 3rd Earl of Essex; but, in Paris, where he arrived early in January 1641, his behaviour belied the pitiful tone of his letters. "He is as merry as if he were the contentedest man living," wrote Aylesbury to Hyde; and the letters of introduction which, in spite of his hasty flight, he had obtained from Charles I and Henrietta Maria, smoothed his way in the French Capital, where he was not likely to be popular on account of his Spanish sympathies. Probably with a view to increasing his difficulties, parliament, in 1642, published an account of an alleged plot hatched by Windebank against the life of Louis XIII and Richelieu because they refused open aid to the Royalists. He also appears to hare had a hand, with his friend, Walter Montagu, in a scheme for rescuing the Earl of Strafford from the Tower of London.

In spite of the dangers on which Windebank dilated to his son, he remained in Paris till his death, with the exception of a visit to England in the Autumn of 1642, when he was refused access to the King at Oxford. He was back in Paris in July 1643, and died there on 1st September 1646, having shortly before been received into the Roman Catholic Church.

By his wife, whose name has not been ascertained, Windebank had a large family. Laud referred, in 1630, to his "many sons". He had five at least, and four survived him. The eldest, Thomas, born about 1612, was intended to follow in his father's footsteps. He matriculated from St. John's College, Oxford, on 13th November 1620, aged 17, but did not graduate. In 1631, his father secured for him the reversion of a clerkship of the signet and, soon afterwards, he entered the service of the Earl Marshal. In 1636, he was travelling in Spain and Italy, whence he returned to take up his duties as clerk of the signet. He was MP for Wootton Basset in the Short Parliament of 1640, sided with the King in the Civil War and was created a baronet on 26th November 1646. He compounded on the Oxford Articles and left a son, Francis, on whose death, in 1719, the baronetcy became extinct. The second son, Francis, was admitted as a student of Lincoln's Inn on 19th March 1633, entered the service of Thomas Wentworth, 1st Earl of Strafford, was made usher of the chamber to Prince Charles, became a colonel in the Royalist Army and was appointed Governor of Bletchingdon House, near Oxford. This, he surrendered at the first summons to the Parliamentary Forces, in April 1645, and was consequently tried by a Royalist Court-Martial and shot. He was married and left a daughter, Frances. Another son, Christopher, born in 1615, was a demy of Magdalen College, Oxford, from 1630 to 1635. He was then sent to Madrid "to understand that court" and lived, for a time, with the English Ambassador, Sir Arthur Hopton. In 1638, he made an imprudent marriage, which cost him his post, and on 5th August 1639, Hopton suggested that his wife should be placed in a convent. Subsequently, being "a perfect Spaniard and an honest man," he was found useful as a guide and interpreter by English ambassadors in Madrid. The fifth son, John, baptised at St. Margaret's, Westminster, on 11th June 1618, was, by Laud's influence, admitted a scholar of Winchester College in 1630. He matriculated from New College, Oxford, on 23rd September 1634, graduated as a BA, on 6th April 1638, and MA, on 22nd January 1642. He was fellow from 1636 to 1643, when apparently he went abroad. He compounded on 9th August 1649, being fined only 10s, and was created MD on 21st June 1654 on Cromwell's letters as Chancellor. In these letters, it was stated that he had spent some time in foreign parts in the study of physic and had practised, for some years, with much credit and reputation. He practised at Guildford and was admitted honorary fellow of the Royal College of Physicians on 30th September 1680. He was buried in Westminster Abbey on 16th August 1704. Of Windebank's daughters, Margaret married Thomas Turner (1591-1672) and was mother of Thomas Turner (1645-1714), President of Corpus Christi, Oxford, and of Francis Turner, Bishop of Ely; Frances married, on 12th July 1669, Sir Edward Hales, titular Lord Tenterden; one died unmarried in Paris about 1650; and two became nuns of the Calvary at the Marais du Temple, Paris