[2] On 11 July 1469, Isabel secretly married George Plantagenet, 1st Duke of Clarence, the younger brother of Edward IV, in Église Notre-Dame de Calais.

[3][4] The marriage was arranged against the King's wishes by her father,[5] and the ceremony was conducted by Isabel's uncle George Neville, archbishop of York.

[6] Following the marriage, Clarence joined forces with Warwick and allied with the Lancastrians led by Margaret of Anjou, queen consort to Henry VI.

After Isabel Neville's sister Anne was married to Edward of Westminster, Prince of Wales, the son and heir of Henry VI, Clarence rejoined his brother, realizing that it was now unlikely that he would become king.

[11] Ankarette's grandson Roger Twynyho received from Edward IV a full retrospective pardon for Ankarette, and the petition he submitted to the king in 1478 describes fully the circumstances of the case, well illustrating the quasi-kingly high-handedness of Clarence, which was ultimately not tolerated by the king:[12] "That whereas the said Ankarette on Saturday, 12 April, 17 Edward IV [i.e.1477], was in her manor at Cayford [i.e. Keyford, Somerset] and Richard Hyde late of Warwick, gentleman, and Roger Strugge late of Bekehampton, co. Somerset, towker, with divers riotous persons to the number of fourscore by the command of George, duke of Clarence, came to Cayforde about two of the clock after noon and entered her house and carried her off the same day to Bath and from thence on the Sunday following to Circeter [i.e. Cirencester], co. Gloucester, and from thence to Warwick, whither they brought her on the Monday following about eight of the clock in the afternoon, which town of Warwick is distant from Cayforde seventy miles, and then and there took from her all her jewels, money and goods and also in the said duke's behalf, as though he had used king's power, commanded Thomas Delalynde, esquire, and Edith his wife, daughter of the said Ankarette, and their servants to avoid from the town of Warwick and lodge them at Strattforde upon Aven that night, six miles from thence, and the said duke kept Ankarette in prison unto the hour of nine before noon on the morrow, to wit, the Tuesday after the closing of Pasche [i.e. Easter], and then caused her to be brought to the Guildhall at Warwick before divers of the justices of the peace in the county then sitting in sessions and caused her to be indicted by the name of Ankarette Twynneowe, late of Warwick, widow, late servant of the duke and Isabel his wife, of having at Warwick on 10 October, 16 Edward IV., given to the said Isabel a venomous drink of ale mixed with poison, of which the latter sickened until the Sunday before Christmas, on which day she died, and the justices arraigned the said Ankarette and a jury appeared and found her guilty and it was considered that she should be led from the bar there to the gaol of Warwick and from thence should be drawn through the town to the gallows of Myton and hanged till she were dead, and the sheriff was commanded to do execution and so he did, which indictment, trial and judgment were done and given within three hours of the said Tuesday, and the jurors for fear gave the verdict contrary to their conscience, in proof whereof divers of them came to the said Ankarette in remorse and asked her forgiveness, in consideration of the imaginations of the said duke and his great might, the unlawful taking of the said Ankarette through three several shires, the inordinate hasty process and judgement, her lamentable death and her good disposition, the king should ordain that the record, process, verdict and judgement should be void and of no effect, but that as the premises were done by the command of the said duke the said justices and sheriff and the under-sheriff and their ministers should not be vexed.