The species is endemic to the southeastern United States, especially in and around the Great Smoky Mountains of eastern Tennessee and western North Carolina.

[2] The latter is distinguished from T. sessile by its larger size, the mottling of its leaves, shorter filaments, the color of its petals, and the character of its stigmas.

[13] T. luteum has been widely introduced elsewhere, with known populations in Maryland, Michigan, Ontario, Pennsylvania, South Carolina, and Virginia.

[17] A few disjunct populations of yellow sessile-flowered trilliums in central Alabama have been identified as T. luteum but botanists disagree on this point.

[19][20] Though hardy down to −15 °C (5 °F), this plant requires a sheltered position with rich, moist leafmould in a shaded, deciduous woodland setting which mimics its native habitat in North American broadleaf forests.