John Clayton was born in 1694 in Fulham, Middlesex, and brought up in comparative wealth until 1715 when he emigrated to Virginia joining his father, John Clayton senior, who became Attorney General for the colony between 1713 and 1737. Disputes over the Clayton estate in England had apparently led John Clayton senior to take a post overseas, initially as secretary to Lieutenant-Governor Edward Nott of Virginia.
John Clayton junior was educated in law and, in 1720, took up a post as Clerk to the County Court of Gloucester County that he was to hold until he was seventy-nine. Soon after taking up the post he married Elizabeth Whiting and they moved into their new residence, believed to have been called Windsor, close to the Pianketank River. Records show they also owned a sizeable garden and plantation, though the precise whereabouts of these and the Clayton home remain uncertain. John and Elizabeth had eight children: five boys, the eldest called John, and three girls.
Clayton's interest in natural history probably stemmed from his friendship with Mark Catesby (1682-1749), the artist and naturalist, who first arrived in Virginia in 1712. Clayton probably joined Catesby on the Spotswood expedition to the Blue Ridge Mountains and later, in about 1734, started collecting material to send to Catesby who by this time was back in England. Catesby in turn passed these specimens on to J.F. Gronovius (1690-1762), and encouraged Clayton to continue sending specimens to Europe. These eventually formed the basis for Gronovius's Flora Virginica (published 1739-1743).
Linnaeus (1707-1778), one of the most revered names in biology, also studied many of Clayton's specimens, and was in close contact with Gronovius. Clayton was also sending seeds as well as dried specimens and some of these found their way to George Clifford's estate, Hartekamp (near Haarlem, Holland), where Linnaeus was working between 1735 and 1737, classifying and describing Clifford's plants. These did not go unacknowledged as Clifford gave a copy of Hortus Cliffortianus to Gronovius with instructions that it should be sent to Clayton. When he received it in 1739, Clayton found that many of his plants had been named and described in it.
Two other notable botanists of the time, and long-distance friends of Clayton, were Peter Collinson (1694-1768), a London mercer with business interests in North America, and his protégé in Philadelphia, John Bartram (1699-1777). Collinson encouraged Clayton to collect mosses and other non-flowering plants, and also introduced him to Bartram who was later (1765) to be appointed the King's botanist. Clayton, disappointed at the lack of recognition that his collecting efforts should have justified, had determined, around 1760, to prepare a new Flora of Virginia. However, the publication of a second edition of Gronovius' flora in 1762 led Collinson to advise Clayton to search for a publisher in America, but none was found and any hope of its publication died with Clayton in 1773.
Much of Clayton's personal effects were lost when the British burnt down the Gloucester County Court House in Virginia where he had worked for so many years, the fire also destroying his house and original collections. Specimens in the herbarium of J.F. Gronovius were purchased by John, Earl of Bute (1778), later purchased from him by Joseph Banks and eventually acquired by BM in 1827. Gronovius named one of Clayton's specimens Claytonia in his honour in 1739. Linnaeus subsequently adopted this generic name and, in 1753, gave the binomial name Claytonia virginica L. to this plant, the well known 'Spring Beauty' of eastern North America.