Copiapoa megarhiza is listed as Endangered because it has an extent of occurrence (EOO) of 273 km². Based on threats, the species is known from five locations, where it is experiencing a continuing decline in the number of mature individuals and habitat quality due to many threats including the development of solar farms, illegal collection and extended droughts. The species is listed here as Endangered.

Copiapoa megarhiza is endemic to Chile, where it occurs in Atacama in the Copiapó valley (Hunt et al. 2006). Historically, it used to be found from east of Paipote to west of Toledo. It grows at elevations of 0 to 800 m asl.

The species has a very patchy distribution, and forms clusters. It can be frequent but is not abundant. Subpopulations have been extirpated in the southeastern part of the range due to mining.

The species grows on coastal hills (lomas costeras) and in Atacama desert habitat. It occurs on very dry granitic hills (Hunt et al. 2006).

The major threats are illegal collection, industry, urbanization and illegal landfills, mainly in the northern subpopulations close to Copiapó. The effect of the extended droughts resulting from the reduction of the length of the camanchaca (coastal fog) season due to climate change is more severe in this species because it occurs further inland and away from the coast. Plants depend on this fog as it is the main source of water. The extended droughts cause a continuing decline in the number of mature individuals throughout the range. Copiapoa megarhiza is also affected by industrialization and its consequences, including road construction. The healthiest population is threatened by the development of photovoltaic farms and their transmission lines. Land use change for pomegranate production is also a threat. Plants and fruit are also affected by insect predation.

There is illegal collection, however, this is very localized with only specific sites targeted.

The species does not occur within protected areas. It is found in 19 ex situ collections (BGCI 2022). It is listed in Appendix II of CITES.