Euphorbia radyeri can be propagated either by seeds or cuttings, with cuttings being the preferred method.

At the Karoo Desert National Botanical Garden, E. radyeri has not yet been propagated by seeds, but other species of Euphorbia, such as E. triangularis and E. ingens are propagated using a specialized soil mixture known as the Karoo mix, which consists of 1 part red soil, 1 part river sand and 2 parts compost, carefully sieved to create a fine, uniform texture that promotes good drainage and aeration. This mix can be used for germinating E. radyeri seeds too. Fill sowing trays with a thin layer of fine bark at the base before adding the growth medium to prevent it from washing out, but also to encourage drainage. Scatter seeds on the growth medium surface, lightly pressing them into the soil to ensure good soil contact, and cover with a thin layer of finely sieved growth medium. Water the trays immediately and place them in a propagation house with bottom heat (where possible) to encourage germination. Ideally, water trays every two days to maintain consistent moisture, but do not overwater. As seedlings develop, watering should be reduced to once a week to prevent rot, since Euphorbia species are sensitive to overwatering. Once strong and healthy (7–8 cm), seedlings are transplanted into individual pots filled with the same growth medium and placed in full sun to harden off after three weeks from transplanting, helping them adapt to outdoor conditions and preparing them to thrive in their natural environment.

To propagate E. radyeri by cuttings, take stem cuttings in spring to early summer when the plant is in its active growth phase. Select a healthy, non-flowering stem and use sterilized pruning shears to make a clean cut just below a node. It is best to take a small, branched stem that has developed from the main stem and remove it from the base node. Since the plant exudes a toxic white latex sap, always wear gloves when handling the cuttings. Place the stem cuttings in a dry, shaded area for five to ten days to allow the wound to callus, reducing the risk of rotting. Once callused, plant cuttings on a raised plant bed filled with a washed coarse river sand. Alternatively, plant pots can be used as containers, using the same medium. Take care to provide balance or support for the cuttings to prevent them from falling over. A rooting hormone may be applied as well, although the cuttings are capable of rooting without it. Ensure that cuttings are placed in a bright area with indirect light and watered sparingly to keep the soil slightly moist but never waterlogged or completely dry. Roots develop within three to six weeks. Once the cuttings are well-rooted, transplant them into individual pots filled with the soil mix described above for seed sowing or any media suitable for succulents with good-drainage and begin the hardening-off process by slowly introducing the plant to full sun, which reflects its natural growing environment.

Euphorbia radyeri grows best in well-drained soil and full sun and should be protected from extreme winds and frost. It is particularly suited to sandy loam soils with rocky particles. A small amount of compost can be added since the plant does not need a lot of organic matter and can grow in poor soils. For successful growth, it is best to transplant young plants while they are still under 30 cm in height. Older plants tend to fall over, which may cause them to die. When planting, take care not to bury the stem, as this can lead to rotting. After planting, water regularly to keep the soil slightly moist until the roots are well established. Once the plant is settled, reduce watering and keep the plants dry during winter. This species also thrives in pots and garden settings. In pots, its bold blue-green columnar stems create a strong architectural statement, requiring minimal care while thriving on little water, and still need to be placed in full sun. In the garden, it is perfectly suited for rockeries and arid beds, where its sculptural form adds dramatic texture and contrast.

Just like other Euphorbia species, E. radyeri is prone to stem rot caused by overwatering and poor drainage, which should always be prevented, as this attracts pests and diseases. Common pests affecting E. radyeri include red spider mites, mealybugs, and white scale. When pests appear, they can be managed with insecticides or neem oil, while small infestations are best controlled by manual removal. To minimize pest problems, ensure that the plant is free from dead or damaged plant material.