Vitis rotundifolia is native to the southeastern United States, growing in dry upland forests, sandy or rocky soils, swamps, and roadsides. Unlike other native grape species, the muscadine has simple, unbranched tendrils, and its fruits appear singly or in small groups rather than in large hanging clusters, ripening to purplish-black or bronze by September and October. The flavor is sweet and distinctly pungent, making the grapes good for eating fresh, drying, and winemaking. Over 300 cultivars are commercially available in the Southeast; the cultivar Scuppernong, named for a river in northeastern North Carolina, is the official state fruit of North Carolina.

The vine is dioecious, meaning that male and female plants are needed for fruit production, though many cultivars carry both flower types and can produce independently. Plant in full sun to partial shade in well-drained soil of almost any type. The dense foliage and climbing habit make it a practical choice for pergolas, trellises, fences, and privacy screens, provided adequate space and light are available. Bees, pollinators, songbirds, and small mammals all use it for food and cover. Its natural resistance to Pierce's disease and the phylloxera insect makes it a valuable commercial crop in regions where those pests devastate other grape species.