After serving as an apprentice to an apothecary, Hill set up his own apothecary shop in London and studied botany in his spare time. Employed by the Duke of Richmond and Lord Petre to arrange their collections of plants, he travelled extensively to collect rare species for them. When these efforts failed to increase his income, he turned to writing plays, novels, and papers on natural history, medicine, astronomy, and geology. He edited the monthly British Magazine from 1746 to 1750 and contributed a daily society-gossip column to The London Advertiser and the Literary Gazette. His satirical writings often involved him in bitter quarrels.

Hill's most lasting work was in botany. In 1759 the first of the 26 folio volumes of his Vegetable System was published. This work, containing 1,600 copper plate engravings, represented 26,000 different plants. Although not completed until 1775, it won for him the Order of Vasa from the king of Sweden. Thereafter he called himself “Sir” John Hill.