[10] Colonial American botanist John Bartram founded the garden on his farm in Kingsessing, west of the Schuylkill River and miles outside and south of the what were then the borders of Philadelphia.

[3] John Bartram (1699–1777), well-known in colonial American as a botanist, explorer, and plant collector, established the garden in September 1728 after purchasing a 102-acre (0.41 km2) farm in Kingsessing Township, Philadelphia County for personal use.

Increasingly he devoted himself to exploration, discovering new specimens and North American species, making substantial scientific achievements.

While Philadelphia operated as the temporary capital of the new nation, prominent visitors to the garden included members of the Continental Congress of 1784 and President George Washington in 1787.

[29] Domestic demand also increased under their management, and they established an additional specimen garden to the west of the Bartram House to showcase popular new flowering plants.

[29] In 1850, financial difficulties resulted in the family selling the historic garden to Andrew M. Eastwick (1811–1879), as a private park for his estate.

Charles S. Sargent of Boston, Massachusetts, who worked at the Arnold Arboretum, helped to organize a national campaign for funds.

[30] Despite the disappearance of a number of subsidiary physical elements in the landscape, the rectilinear framework that John Bartram designed and laid out in the eighteenth century can still be recognized.

A small number of examples in the garden's plant collection date from the Bartram family occupancy;[30] however, documentation for what was once in cultivation is rich.

[33] Bartram's Garden's long existence as a living botanical space, its focus on native plants, and its resonance with the surrounding area's history make it an unparalleled site for presenting and interpreting eighteenth- and nineteenth-century botanic and agricultural studies, the development of the field of botany, the plant and seed business in North American, the lives of John Bartram and his family, and domestic life in Philadelphia.