Leader of Jacobites
At the start of the reign of the Hanoverian King George I (1714–1727), Bolingbroke fled into exile in France to join the court of the Old Pretender, and Wyndham took his place in England as the leader of the Jacobites. A rebellion to oust King George was planned for the summer of 1715, and Wyndham sent a message to the Pretender in July "not to lose a day in going over". However, the rebellion was discovered and Wyndham's role was laid before the cabinet, attended by both the king and the 6th Duke of Somerset, Wyndham's father-in-law, who although a member of the Whig government and a firm supporter of the Hanoverian Succession, wanted to protect his son-in-law from arrest, and thus volunteered to "be responsible for him". Most ministers were inclined to agree to this for fear of offending a person of such consequence, yet Lord Townshend, Secretary of State for the Northern Department, in the belief that the government needed to show firmness, moved the motion to have him arrested. Ten minutes of silence ensued while the other ministers considered their own responses, and finally two or three others seconded the motion and the arrest was decreed by the king, who on retiring to his closet took Townshend's hand and told him: "you have done me a great service today".
Lord Stanhope brought down to the Commons a message from the King, desiring their consent for apprehending six members of their House on a charge of "being engaged in a design to support the intended invasion of the kingdom", namely Sir William Wyndham, Sir John Pakington, 4th Baronet, Edward Harvey (MP for Clitheroe), Thomas Forster, John Anstis, and Corbet Kynaston. Consent was granted. Harvey and Anstis were in London, and were at once taken. Harvey stabbed himself in the breast in two or three places but his wounds were not mortal. Forster escaped and served as General of the Jacobite army in the 1715 Uprising.
Accordingly, Colonel John Huske of the "foot-guards" (i.e. Coldstream Guards), at about this time an aide-de-camp to William Cadogan, 1st Earl Cadogan, was sent to arrest Wyndham at home at Orchard Wyndham. The story is related in detail by the contemporary commentator Boyer (1716). He was awoken at 5 in the morning and on searching his bedroom the colonel found incriminating papers in his waistcoat pocket, which listed his co-conspirators who planned to invade England and place the Old Pretender on the throne. The colonel had orders to "use him with decorum" and trusted Wyndham when he gave his word that at 7 am, having dressed and said goodbye to his pregnant wife, he would be dressed and ready to depart as the colonel's prisoner, and would even lay on his own coach and six horses for the purpose. Wyndham however escaped by the third unguarded door of his chamber and fled, it is said by having jumped out of a window onto a waiting horse. This caused the king to circulate a hand-bill headed "Proclamation for apprehending Sir William Wyndham, Baronett", dated 23 September 1715, which offered a huge reward of £1,000 for his capture.
Seeing that his case was hopeless, having for a while disguised himself as a clergyman, he visited his father-in-law the Duke of Somerset at his seat of Syon House, near London. From there he went to London and surrendered himself to the Duke's son and his brother-in-law the Earl of Hertford, a captain in the King's Lifeguards, and was taken into custody in the Tower of London. The 6th Duke of Somerset offered bail to the council for Wyndham's liberty, which was refused. It was soon after having made that offer that the king dismissed him from the high office of Master of the Horse.
Under King George I (1714–1727) and during the early years of King George II (1727–1760) Wyndham was the leader of the Tory opposition in the House of Commons and fought for his High Church and Tory principles against Sir Robert Walpole. He was in constant communication with the exiled Bolingbroke and after 1723 was actively associated with him in abortive plans for the overthrow of Walpole.