Euphorbia makallensis is a succulent shrub endemic to Ethiopia, where it is only known from a very restricted area in Tigray floristic region. It occurs at two locations, one near the town of Igre Hariba east of Mekele and the second c. 75 km north near Hawzen. The extent of occurrence (EOO) is estimated as 42 km² and the area of occupancy (AOO) is estimated as 8–12 km². Despite its highly restricted range, there is no evidence of ongoing decline in the population, distribution, or area of suitable habitat for this species. It is abundant in grazed areas which have not changed significantly in size or distribution since this species was first discovered in 1975. As such, it does not meet the requirement of continuing decline for criterion B. It is apparently common within its limited range, although the population size and current trend, as well as generation length, could not be calculated: criteria A and C could therefore not be applied. Despite a lack of evidence for historical or current declines, urbanisation of the nearby city Mekele is occurring rapidly and it is likely that the location near Igre Hariba will be impacted in the near future. It is plausible that this species could be pushed to Critically Endangered in a short period of time if this location were lost to urbanisation. Given the presence of a plausible future threat that could rapidly affect the extinction risk of the species, it qualifies as Vulnerable D2.

This species is endemic to Ethiopia (Gilbert 1995), where it is only known to occur at two disjunct locations in Tigray floristic region. One location is at the village of Igre Hariba near Mekele and the other is c. 75 km to the north near Hawzen. At Igre Hariba, this species occurs over an area of c. 4 km² (Carter et al. 1981) and while the total occupied area at the northern site is not known, it is inferred to be similar (Wilson and Munro 2019). As such, the extent of occurrence (EOO) is estimated as 42 km² and the area of occupancy (AOO) as 8–12 km².

This species is locally abundant at both of its two known locations. Within the c. four km² area over which it occurs near Igre Hariba, the density of plants was estimated as ranging from 885–10,400 plants per hectare in the uncultivated, rocky or steep areas used for livestock grazing (Carter et al. 1981). The subpopulation near Hawzen is reported to have a similar population structure and abundance (Wilson and Munro 2019).

This species is a low-growing succulent shrub with densely packed stems up to 50 cm high, forming large cushions up to 1.5 meters across (Gilbert 1995). It occurs in grazed scrub vegetation on steep slopes and in rocky areas. It is absent from flatter areas with deep soil, presumably because it has been removed for crop cultivation here (Carter et al. 1981).

Euphorbia makallensis is locally abundant in grazed areas around Igre Hariba and does not appear to be negatively impacted by livestock grazing. While it is likely removed from arable land and cultivated areas (Carter et al. 1981), it is not typically disturbed otherwise (Wilson and Munro 2019). A visit to this population in 2018 found that the spatial distribution and age classes of plants was similar to that observed when discovered in 1975, suggesting that the population and area of suitable habitat for this species has not declined significantly in this time (Wilson and Munro 2019). However, it should be noted that the city of Mekele is expanding rapidly and future urbanization may impact E. makallensis. Urban expansion surrounding Mekele has largely been occurring to the north of the city, whereas the area southeast of the city where Igre Hariba is located has so far seen lower levels of urbanization due to the hillier terrain (Fenta et al. 2017). However, it is expected that urbanization towards Igre Hariba, as well as expansion of the town itself, will increase in the near future. A campus of Mekele University has recently been constructed less than a kilometre from the core of this species' extremely limited range at this location. Alula Aba Nega Airport is also located fewer than three kilometres from Igre Hariba. The site near Hawzen is less likely to be potentially threatened by urbanization due to its lack of proximity to any large cities or towns.

This species is grown as an ornamental by specialist collectors. Like other Euphorbia species, it may also have medicinal uses.

All succulent Euphorbia species are included in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). There are no species-specific management plans in place for Euphorbia makallensis and it is not known to occur in any protected areas (UNEP-WCMC and IUCN 2023). It is common in cultivation and is held in several ex situ conservation collections (BGCI 2023).