The Civil War marked a great turning point in the history of the college. Windsor Castle was occupied by the forces of Parliament on 23rd October 1642 after the Battle of Edgehill. In a spirited, but useless, act of defiance the then Dean, Christopher Wren, the father of the great architect, refused the Parliamentarian captain the keys of St George's. In response his troops broke open the chapel and treasury and plundered them. More destruction followed in 1643 when vestments, glass, hangings and metalwork, including elements from Henry VIII's unfinished funeral monument, were pillaged or broken. Lead was also stripped off the chapel roofs leaving the fabric exposed to the weather. The college buildings suffered badly too, portions being pressed to use as a prison and others pillaged for their materials. Some were completely destroyed at this time including the 15th-century chapter house, which stood to the west of the Dean's Cloister.

Charles I was executed in 1649, wearing two shirts lest his shivering in the cold should be mistaken for fear (one shirt is now in the Royal Library). The King's burial was one of the more dramatic scenes in the history of St George's. He was brought to the looted chapel in thick falling snow and lowered into a small vault in the centre of the choir, which already contained the coffins of Henry VIII and Jane Seymour. When this vault was opened in December 1888, for the return of some relics, the black velvet pall, probably given by a Royalist, was still resting on the coffin.

Following the Restoration of the monarchy the repair of the buildings began. It was a long and protracted affair running into the 1680s. The canons provided much of the money for the work and the buildings of the college were extensively restored.

Of the Hanoverian kings, George III was the most active in the affairs of St George's. During the 1780s and 1790s, he was exceptionally generous to the chapel, causing the woodwork in the choir to be repaired and adding more Garter stalls. He provided a magnificent new organ as well as a new altar reredos and east window incorporating painted glass by Benjamin West. He also ordered the erection of the present choir screen between 1790-2, a structure made of artificial Coade Stone. The craftsman responsible for this work was the architect to the Dean and canons, Henry Emlyn. His work is in a Gothic style which brilliantly captures the flavour of the late medieval art and architecture within the chapel. George III also arranged for the excavation of the Royal Vault under the Albert Memorial Chapel, in which several monarchs and members of the Royal Family are laid to rest.

King George IV caused a memorial to his daughter, Princess Charlotte, who died in childbirth in 1817, to be placed in the Urswick Chapel. This meant the removal of the memorial screen erected by Dean Urswick, which was replaced in the restoration of 1920-30. The memorial was executed by Matthew Wyatt.

The funerals of George III, George IV and William IV all took place in the chapel, and in those days it was the custom that the new monarch did not attend, so as to avoid an association with death.