Claypole married Elizabeth, Oliver Cromwell's second daughter, before October 1646, and raised a troop of horse for Parliament to oppose Charles II in 1651.

[6] Mark Noble speculates that the sentiments the father entertained respecting the state of the nation was probably the same as that which Oliver Cromwell possessed, when he first gained a seat the Long Parliament; and as John Claypole had suffered hardships during King Charles I's Eleven Years' Tyranny, it might occasion an intimacy that ended in an alliance between the families.

[9] On 11 August 1651, during the Third Civil War, he received a commission from the council of State to raise a troop of horse in the counties of Northamptonshire and Lincolnshire to oppose the march of Charles II into England.

Ludlow said: Mr. Cleypoole stood up in the house, which was unusual for him to do, and told the house, he could but start the game, and must leave it to them that had more experience to follow the chase, and therefore should only say, that he had formerly thought it necessary, in respect of the condition in which the nation had been, that the major-generals should be entrusted with the authority which they had exercised but in the present state of affairs, he conceived it inconsistent with the laws of England, and liberties of the people, to continue their power any longer.

[14][15]Claypole was appointed by his father-in-law one of the lords of his bed-chamber, clerk of the hanaper, and ranger of Whittlewood Forest in Northamptonshire, where he built Wakefield Lodge, a magnificent house near Potterspury.

Mrs. Hutchinson terms him "a debauched ungodly cavalier",[f] and in the Second Narrative of the late Parliament he is described as one "whose qualifications not answering to those honest principles formerly so pretended of putting none but godly men into places of trust, was for a long time kept out".

[20] Samuel Pepys mentions a famous running footman who had been in Claypole's service,[21] and Clapole also asked Colonel Verney for a dog of superior fighting capacity.

Instead therefore, of appointing Claypole to be a major-general, where severity and rigour was necessary, Oliver gave him places of great honour and emolument, but of such a nature as that the most scrupulous might accept.

[25][5][h] Some years afterwards, however, when court and country were filled with rumours of plots, Claypole was fixed upon to be the head and contriver of one against the royal family, supposedly in consort with the old Oliverian party.

Claypole was therefore remanded back to the Tower; but at the next term, as no evidence appeared against him, and what was, perhaps, much more fortunate to him, a counter plot began to work, he was discharged.

Other brothers included Edward (1636 – c. 1690), a Captain of Foot, who resided in Barbados from the late 1660s/early1670s and Norton (1640–1688), who emigrated to North America in 1678 and died there in Sussex County, Delaware.