In 1686 (settlement dated 16 June) he m. Mary, daughter of Sir Herbert Evans of Gnoll, Neath, Glam., who became her father's sole heiress on the death of her sisters. (She herself d. before July 1696). On his marriage, Mackworth settled at Neath. His wife's grandfather, David Evans, as well as her father, had obtained leases which virtually gave them a monopoly in the working of coal in this area. These were renewed for Mackworth, who actively developed coalmining on his wife's estates. Copper smelting had been carried on at Neath in the late 16th cent., and may have been continued spasmodically in the 17th cent. Local coal had been used from the start to smelt copper there and in Cornwall, and on this account Mackworth became interested in copper smelting. He may have started smelting at Neath as early as 1695. In 1698 he acquired large interests in Cardiganshire. Rich mineral deposits had been found in 1690 on the Gogerddan estates, and a company had been formed by Sir Carbery Pryse (see Pryse of Gogerddan) to develop them. This became increasingly important in 1693 when the monopoly of the Society of Mines Royal was terminated. After Sir Carbery Pryse's death (1694) Mackworth, in 1698, acquired his interests for £16,440, and reorganised the enterprise as the Company of Mine Adventurers, which obtained its charter in 1704. Rapid development in smelting then took place at Neath, which was centrally situated between Cardigan and Cornwall, the two sources of mineral supply. Mackworth was, however, engaged in bitter disputes with neighbouring coal proprietors, notably Sir Edward Mansel of Briton Ferry (see Mansel family), and his Company of Mine Adventurers, which had been financed by very dubious means, became bankrupt in 1709. This matter was investigated in 1710 by a committee of the House of Commons, which declared Mackworth ‘guilty of many notorious and scandalous frauds,’ but he was saved by the fall of the Whig administration in that year. In 1713 he formed the Company of Mineral Manufacturers, but this ceased operations in 1719, although smelting continued at Neath until his death. In 1715 he acquired various manors at Neath.

Mackworth sat in parliament as member for Cardiganshire in 1701, and from 1702 to 1705. He then abandoned Cardiganshire for Oxford University, but was defeated, and sat for Totnes from 1705 to 1707. He wished to be returned for Cardiganshire in 1708, but Lewis Pryse of Gogerddan was himself a candidate. Mackworth therefore contested Cardigan boroughs at a by-election in Feb. 1710, but the financial scandal was then at its height, and he was defeated. He was once more returned for the shire in Oct. 1710, and sat until 1713. He was an active member and served on an unusually large number of committees. His political views were typical of the Tory High Church party, and, despite his Puritan ancestry, he was a strong supporter of the Occasional Conformity Act.

He was one of the four laymen who assisted Dr. Thomas Bray to form the S.P.C.K. on 8 March 1699. In 1706 his company made provision for the payment of £20 a year towards a Charity school at the Esgair Hir mine in Cardiganshire, and £30 a year to a minister at the same place, as well as £20 a year towards a Charity school at Neath. On 17 Sept. 1719, in view of the difficulty of getting a schoolmaster at Neath, he suggested to the S.P.C.K. the use of an ‘itinerant master’ to start new schools and train ushers in them. He wrote a number of religious works. His piety and benevolence are in strange contrast to the dubious nature of his financial transactions. He d. on 25 Aug. 1727.