The cultivation of Amaryllis belladonna requires very little attention. Amaryllis belladonna can be grown from seed. The soft fleshy white to pink seed should be planted when fresh. Dispersal of seed in winter is normally by wind. Seed dispersal is timed to coincide with the first winter rains in late March and April. Germination can occur in two weeks, but seedlings require three to six years or longer to flower. Large clumps of bulbs can be divided from the mother bulb during the dormant period. The bulbs and offsets can be planted immediately. The bulbs must be planted with their necks at soil level. The belladonna lily can also be grown in large pots using a very porous soil mix. The bulb can also tolerate quite arid conditions. In cultivation flowers are produced almost every year but in the fynbos they emerge prolifically after fires.

 Amaryllis belladonna is often attacked by a highly destructive black and yellow striped caterpillar called lily borer. The caterpillar bores into the leaves and stem of the lily causing the flowering stem to collapse. The caterpillar eventually enters the bulb. The caterpillars can be removed by hand or the affected foliage can be cut off.