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Born in 1644 or 1645, at Pritchard's Alley, Fair Street, Horselydown, Southwark the eldest child of Thomas Guy, lighterman and coalmonger, also described as citizen and carpenter. His father, an anabaptist, died When Thomas was eight years old. His mother returned to her native place, Tamworth, Staffs, where she married again in 1661. Thomas Guy was educated at Tamworth. In 1660 he was apprenticed for eight years to John Clarke, bookseller, in Mercers' Hall Porch, Cheapside, London. At the end of his apprenticeship, 1668, he was admitted by servitude a freeman of the Stationers' Company, and of the city, in 1673 he was admitted into the livery of the Stationers' Company. In 1668 he set up in business as a bookseller in the corner house at the junction of Cornhill and Lombard Street, with a stock worth about £200. At this time there was a large unlicensed traffic in English bibles printed in Holland, in which Guy is said to have joined extensively. The king's printers had complained of the infringement of their privilege, and made numerous seizures of Dutch printed bibles. At the same time they were underselling the universities, and trying to drive them out of competition. Before 1679 Guy and Peter Parker came to the aid of Oxford University and became university printers, in association with Bishop Fell and Dr Yates. They printed at Oxford numerous fine bibles, prayer-books, and school classics, and effectually checkmated the king's printers, both in litigation and in business. But certain members of the Stationers' Company succeeded in ousting them from their contract in 1691-2, after a sharp contest. Guy imported type from Holland and sold bibles largely for many years. He also published numerous other books. Having accumulated money he invested it in various government securities, and especially in seamen's pay-tickets. In 1695 Guy became member of parliament for Tamworth, where he had in 1678 founded an almshouse for six poor women, enlarged in 1693 to accommodate fourteen men and women. Guy sat until 1707, when he was rejected, and declined a request from his constituents to stand again. Guy early became somewhat noted as a philanthropist. He had maintained his almshouse in Tamworth entirely himself, and among other benefactions to Tamworth he built a town hall in 1701, which is still standing. Many of his poor and distant relations received stated allowances from him. He spent much money in discharging insolvent debtors and reinstating them in business, and in relieving distressed families. In 1709 he contributed largely for the poor refugees from the palatinate; and often sent friendless persons to St Thomas's Hospital with directions to the steward to give them assistance at his own cost.
In 1704 Guy became a governor of St. Thomas's Hospital, and thereafter was one of its principal and active managers. In 1707 he built and furnished three new wards in the hospital for sixty-four patients, at a cost of £1,000, and from 1708 contributed £100 yearly towards their support. He also improved the stone front and built a new entrance from the Borough, and two new houses at the south-west of the hospital.
In 1720 Guy is said to have possessed £45,500 of the original South Sea Stock. The £100 shares gradually rose. Guy began to sell out at £300, and sold the last of his shares at £600. Having thus a vast fortune he decided to carry out a project long contemplated, of providing for the numerous patients who either could not be received in St. Thomas's Hospital, or were discharged thence as incurable. He consequently in 1721 took a lease from the St. Thomas's governors of a piece of ground opposite the hospital for 999 years, and, having pulled down a number of small houses, began the erection of a hospital on the site in 1722, intending to place it under the same administration. When the building was raised to the second story, he changed his mind and decided to have a separate government. The building, which cost £18,793, was roofed in before the founder's death, which took place on 27 Dec 1724 in his eightieth year.
Guy's will was signed on 4 Sep 1724, and bequeaths lands and tenements in Staffordshire, Warwickshire, and Derbyshire to grandchildren of his deceased sister, about £75,000 in four per cent annuities, mostly in sums of £1,000 to about ninety cousins in various degrees, as well as some persons apparently not relatives, and annuities varying from £10 to £200 per annum to others, mostly older relatives, being the interest on about £22,000 stock. One thousand pounds was left to discharge poor debtors in London, Middlesex, or Surrey, in sums not exceeding £5 each. Four hundred pounds per annum was left to Christ's Hospital for the board and education of four poor children annually, to be nominated by the executors, the governors of Guy's, with preference to Guy's relations. His almshouse and library at Tamworth was left in trust for the maintenance of fourteen poor persons of parishes surrounding Tamworth, excluding the town itself, preference being given to his own poor relations, a portion of the endowment being applied to apprenticing children, and nursing four, six, or eight persons of the families of Wood or Guy; while £1,000 was left to other persons for charitable purposes. The remainder of his fortune, amounting to more than £200,000, was left to Sir Gregory Page, bart., Charles Joye, treasurer of St. Thomas's Hospital, and several other of its governors, including Dr. Richard Mead, to complete his hospital for four hundred sick persons who might not be received into other hospitals from being deemed incurable, or only curable by long treatment; lunatics, up to the number of twenty, were to be received for similar reasons; but full discretion was given to the executors for varying the application of the funds. The executors and trustees were desired to procure an act of parliament incorporating them with other persons named, all governors of St. Thomas's, to the number of fifty, with a president and treasurer; they were to purchase lands, ground rents, or estates with the residuary estate, and maintain the hospital by the proceeds, any surplus to be applied to the benefit of poor sick persons or for other charitable uses. The required act of parliament was obtained in the same year (11 George I, cap. xii.), and gave power to the executors to set up a monument to Guy in the chapel.