Euphorbia sekukuniensis grows slowly and thrives in hot climates and is also resistant to light frost. Plants can easily be propagated sexually (by seeds) and asexually (by cuttings). Coarse river sand is an ideal medium for sowing the seeds and rooting cuttings.

Propagation from seeds is done in autumn (from February to April) and cuttings are taken in late summer and in spring. Keep in a warm, moist area. When propagating from cuttings it is important to leave the cuttings for about 3 to 4 days for the milky latex to dry, before putting the cuttings into the medium. Keep the soil moist, not wet to avoid rotting. Use coarse bark at the bottom of the seedling tray or pot to improve water drainage.

This species grows very well in full-sun positions, in rocky areas such as rock gardens. Water the plants in summer and keep them dry in winter.  Other Euphorbia species that best complement E. sekukuniensis include, E. ingens, E. cooperi, E. triangularis, E. grandicornis, E. tetragona and E. grandidens, and small succulent plants such as species of Aloe, Crassula, Cotyledon, Tylecodon,  Cyphostemma, Gasteria, Cheriodopsis, Kalanchoe, Cyphostemma, Adromischus, etc.