Plant in full to part sun. Well-drained soil is ideal. Moderate water when established. Hardy to 10°F.

This species is a larval host plant for the Henry's Elfin, and Holly Azure butterfly. Butterflies and other pollinators use the flowers for nectar. The fruits are eaten by many species of birds and small mammals. Also provides winter cover. Members of the genus Ilex support the specialized bee, Colletes banksi.

This plant was traditionally used by Native Americans to make an infusion containing caffeine. It is only one of two known plants endemic to North America that produce caffeine. The other (containing 80% less) is Ilex cassine, commonly known as dahoon holly. Yaupon is also widely used for landscaping in its native range. The young leaves are picked, browned and dried in an oven, steeped in hot water and used to make the tea. This species is related to the plant that makes yerba mate, Ilex paraguayensis. The fruits of this plant are not edible for people.

Ilex in Latin means the holm-oak or evergreen oak (Quercus ilex). Despite the Linnaean classification of Ilex as holly, as late as the 19th century in Britain, the term Ilex was still being applied to the oak as well as the holly – possibly due to the superficial similarity of the leaves. The species name, vomitoria, is a misnomer and refers to the mistaken reputation for this plant causing vomiting—at one point Europeans witnessed a ceremony with the tea of this plant where vomiting was the result—the cause was not from the tea, however. The common name, yaupon holly, derives from a Catawba word, most likely yap, yop, yą (“tree”), with the second element being either a diminutive suffix or pą (“leaf”) (resulting in the compound yąpą); alternatively, perhaps directly from a longer form of the word for leaf, 'yap'hâ.

Yaupon holly occurs in the United States from the Eastern Shore of Virginia south to Florida and west to Oklahoma and Texas. A disjunct population occurs in the Mexican state of Chiapas.