Mesophotic coral ecosystems (MCEs; ~30–150 m depth) are among the most biologically diverse and least protected ecosystems in the world's oceans. However, discussions regarding the conservation of these unique ecosystems are scarce. To address this issue, we identified the features of MCEs that demonstrate they should be considered as a global conservation priority. Some MCEs are characterized by their well-preserved and unique seascapes; their narrow environmental tolerance and high vulnerability to anthropogenic effects; and their slow recovery and reduced reproductive performance. The unique biodiversity of MCEs includes depth-adapted specialist species and new species, most of which are threatened or important fishery resources. MCEs also provide refuge against human stressors, valuable ecosystem services, and ecological connectivity. MCEs generally meet the criteria to be classified as Ecologically and Biologically Significant Marine Areas under the Convention on Biological Diversity. However, we highlight that many MCEs worldwide are threatened and not yet adequately protected by fishery regulations, marine protected areas, or considered in marine spatial planning. Establishing MCEs as a global conservation priority requires the designation of national, international, transnational, public, and private policies.