Although professionally better known for his work on North American cactus, grapes and wine formed the longer and arguably more culturally important thread of U.S. botanist George Engelmann's (1809–1884) career. Through new and comprehensive use of Engelmann's personal papers, letters, and informal daily correspondence housed at the Missouri Botanical Garden, this essay offers a reappraisal of the botanist's place in the history of grape science, the international wine industry, and the late 19th-century phylloxera crisis, as well as the use of wine in his medical practice in St. Louis. Engelmann's work on Vitis L. illustrates that he served as the hub of a wide wheel of scientific inquiry, positioning U.S. botanists as experts for prestigious international audiences. His contributions in three related arenas—botanical discovery and naming of Vitis species, service to the wine industry, and as a physician attending to St. Louis families' health by prescribing wine—were all crucial facets of U.S. national expansion. Like many other wine enthusiasts, Engelmann and his adopted countrymen were interested in defining U.S. viticulture and the nation itself as projects concerned with both wild, resilient native stock and cultivated refinement.