It is native to the southeastern United States but is especially common in a region that extends from southern Kentucky through central Tennessee to northern Alabama.

[7] In its native habitat, this perennial plant flowers from early March to late April (depending on latitude).

[3] The specific epithet cuneatum, which means "narrow below and wide above, wedge-shaped",[14] refers to the tapered shape of the basal half of its flower petal.

[9] As of February 2022[update], Kew's Plants of the World Online accepts no infraspecific names for Trillium cuneatum.

[4] Some authorities recognize the name Trillium cuneatum f. luteum J.D.Freeman,[19] a form marked by the absence of purple pigments from all floral parts.

[20] Trillium cuneatum is endemic to the southeastern United States, ranging from Kentucky southward to southern Mississippi, and to the eastern coast of South Carolina.

[21] There are hundreds of observations of T. cuneatum made by citizen scientists outside of its native range, in more than a dozen states, but especially in Virginia, Pennsylvania, Maryland, and New York.