Although the historic range of relict trillium is unknown, the existing populations were probably much larger. Relict trillium thrives best in mature, moist, undisturbed hardwood forests. Most sites are free from fire. The soils on which this plant occurs range from alluvial sands to rocky clays, but they all have a high organic content in their upper layer. Most relict trillium sites are threatened by logging, road construction, agricultural conversion, or residential and industrial development.
Many sites are close to expanding urban areas.
Some sites are being converted for pine monoculture, pastures, or row crops. Stone quarrying has adversely impacted at least one population, and stone, clay, or sand quarrying is a potential threat to a few others. Two human-introduced, weedy vines are also a serious threat. Japanese honeysuckle and kudzu are encroaching on relict trillium at many of its sites. This site, located in Aiken and Edgefield Counties, South Carolina, is owned by private, State, and municipal landowners.