Butterfly milkweed grows in dry, sunny, well-drained open ground in eastern North America. VASCAN records it as native in Ontario and Quebec. It is a larval host for monarch and queen butterflies and several moths, though monarchs are reported to prefer other milkweeds, likely because of its rough leaves and low cardenolide content. It also feeds native bees, bumble bees and hummingbirds.
The genus is named for Asclepius, the Greek god of healing, and tuberosa refers to the tuberous root. Its older English name pleurisy root comes from historical medicinal use by Native Americans and settlers. The fibre from the seed pods was spun into candle wicks.