Sassafras should be grown in full sun or partial shade, preferably on moist, well-drained acid soil but it will tolerate drier, rocky sites, where it is sometimes found in the wild. It often forms thickets in old fields perhaps due to an allelopathic chemical produced by the tree – Boxelder, elms, and Silver Maple are known to be sensitive to this chemical.

Stunning yellow , red, or orange fall colors are displayed on trees grown in the full sun. Reportedly difficult to transplant due to its long tap root and unbranched root system on well-drained soils. There are usually only a few, but they are large, lateral roots. This problem can be somewhat overcome by purchasing trees grown in root-pruning containers but even container-grown plants can have a sparse root system. Prune early in the life of the tree to form a single trunk suitable for urban landscape planting, or grow with multiple trunks for a dramatic specimen. Many root sprouts often occur beneath the canopy producing a clump of many trees without mowing or pulling up the sprouts.

Plants serve provide nectar for butterflies and are hosts for spicebush swallowtail (Papilio troilus) and the palmedes swallowtail (Papilio palamedes) butterfly larvae. Plants root from root cuttings. Fruits occur on female trees only.