Whorled milkweed is an herbaceous perennial, usually unbranched but occasionally with a few branches toward the tip. Sap is milky. Flowers in the typical milkweed form, in small umbels arising from upper leaf nodes, white to greenish white, with 6–20 flowers per umbel. Blooms May–September. Leaves threadlike, soft, to 2 inches long, arising from many whorls on the stem, with 3–6 leaves per whorl. Fruits smooth, narrow pods less than 4 inches long, erect, bearing seeds that have a tuft of white hairs.
Similar species: Another Missouri milkweed, fourleaf milkweed (Asclepias quadrifolia) is also called whorled milkweed. It looks much different, with 2 or 4 lance-shaped to ovate leaves per node, and often has pinkish flowers. Also, it lives in open woods instead of upland prairies.