During the Civil War he became prominent as Sergeant Major General of the Parliamentary forces in North Wales. In the summer of 1642 he was sent to his constituency to exercise his influence on behalf of the Parliament, and accordingly, in December 1642, he addressed to his countrymen a letter with strong advice to submit to and assist Parliament. By the king's order, Colonel Robert Ellice of Gwasnewydd, near Wrexham, seized Myddelton's residence, Chirk Castle, in his absence in January 1643. A garrison was placed there under Sir John Watts.