On 11 July 1469, George married Isabel Neville, elder daughter of Richard Neville, 16th Earl of Warwick ("Warwick the Kingmaker"). Following her father's death, Clarence was jure uxoris Earl of Warwick.
Clarence had actively supported his elder brother's claim to the throne, but, following his marriage, he began to play a dangerous game. When his father-in-law, the Earl of Warwick, became discontented and jealous, and deserted Edward to ally himself with Margaret of Anjou, consort of the deposed King Henry, Clarence joined him in France, taking his pregnant wife, Isabel. She gave birth to their first child, Anne, (who died shortly afterwards) on 16 April 1470, in a ship off Calais.
After a short time, Clarence realised that his loyalty to his father-in-law was misplaced: Warwick married his youngest daughter, Anne, to Edward of Westminster, King Henry VI's heir. Since it now seemed unlikely that Warwick would replace Edward IV with Clarence, Clarence changed sides. Henry VI rewarded Clarence by making him next in line to the throne after Edward of Westminster (justifying the exclusion of Edward IV either by attainder for his treason against Henry or on the grounds of his alleged illegitimacy).
Warwick's efforts to return Henry VI to the throne having failed, and Warwick himself having been killed in battle, George was restored to royal favour, but now saw his main rival as his younger brother, Richard Plantagenet, 1st Duke of Gloucester, who had married the widowed Anne Neville. In 1475, his wife Isabel, Anne's sister, finally gave birth to a son, Edward, later Earl of Warwick.
Like the first lords of Richmond, Peter II of Savoy and Ralph de Neville, 1st Earl of Westmorland before him, George was endowed with the lordship of Richmondshire but without the peerage.
The Neville sisters were heiresses to their mother's considerable estates, and their husbands vied with one another for pride of place, with Richard eventually winning out. Clarence, who had made the mistake of plotting against his brother Edward IV, was imprisoned in the Tower of London and put on trial for treason. Following his conviction, he was "privately executed" at the Tower on 18 February 1478, and the tradition grew up that he had been drowned in a butt of Malmsey wine.
The tradition may have originated in a joke, based on his reputation as a heavy drinker. However, a butt was equal to three hogsheads—105 imperial gallons— (477.3 litres) enough to easily drown in. A body, believed to be that of Clarence, which was later exhumed, showed no indications of beheading, the normal method of execution for those of noble birth at that time. Another possibility is that George's remains were sent to the abbey in a barrel of Malmsey, as Horatio Nelson's were sent home in a barrel of brandy.
Clarence's wife, Isabel, had died in 1476, two months after giving birth to a short-lived son, Richard (6 October 1476 - 1 January 1477), and they are buried together at Tewkesbury Abbey in Gloucestershire. Their surviving children, Margaret and Edward, were cared for by their aunt, Anne Neville, until she died in 1485, when Edward was 10 years old.
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