Thomas was educated at Balliol College, Oxford, 1615, and Lincolns Inn, 1616, and in 1629 m. Margaret, daughter of Sir Robert Napier of Luton and sister-in-law of Sir Thomas Myddelton (1586-1667) (q.v.); but the suggestion (D.N.B., xl, 16) that his parliamentary sympathies arose from this source seems unnecessary in view of the strength of Puritan feeling round Oswestry and in his mother's family. On the outbreak of war he was given a colonelcy in the parliamentary army, and conducted a successful campaign on the Salop-Denbighshire border, being instrumental in the capture of Wem (11 Sept. 1643), Oswestry (23 June 1644) and eventually Shrewsbury (22 Feb. 1645). On 12 May 1645 he succeeded Sir Thomas Myddelton as commander-in-chief for North Wales, with the rank of general, and after preventing the relief of Chester by defeating Sir William Vaughan near Denbigh (1 Dec. 1645) he reduced successively the royalist garrisons of Ruthin, Caernarvon, Beaumaris, Conway, Denbigh (1646), Holt and Harlech (1647), thereby completing the subjection of North Wales to parliament. On 30 Dec. 1647, he was awarded £5,000 out of delinquents’ estates and the office of vice-admiral of North Wales. In the second Civil War he scotched the rising of Sir John Owen (1600-1666) (q.v.), defeating him in a seashore skirmish at Y Dalar Hir, Llandygái (5 June 1648), and reducing Anglesey to subjection after the recapture of Beaumaris castle (2 Oct. 1648). On 25 June 1651 he was added to the high court of justice set up by the Rump for the trial of delinquents, and in the same year he was a member of the court martial at Chester which condemned the earl of Derby. From 1647-52 he served frequently as commissioner for taxes and militia in the North Wales counties; he represented Salop in the first Protectorate parliament (1654) and was county commissioner there for the decimation tax in Dec., 1655. He d. the following Nov. His letters suggest a man of humane and generous temper, and archbishop John Williams (q.v.) says he was ‘well-beloved’ in North Wales (Cal. Wynn Papers, 1834); but the treatment of Irish prisoners taken at Conway is a blot on his reputation.

Another branch of the family, descended from a younger brother of Thomas Mytton's great-grandfather, acquired land in Montgomeryshire, intermarried with the Devereux of Vaynol (q.v.), and founded the family of Mytton of Garth.