Soil plays a significant role in controlling the global carbon (C) cycle. Studies on climate change mitigation have focused entirely on soil organic carbon (SOC) to increase C sequestration and decrease carbon dioxide (CO2) emissions. In contrast, the contribution of soil inorganic carbon (SIC) to CO2 emissions is usually neglected because SIC is generally considered to be very stable. However, the significant worldwide increase in soil acidification, mainly because of intensive N fertilization and high atmospheric deposition, causes a considerable decrease in SIC stocks, leading to very high unaccounted CO2 efflux. Additionally, large areas of acidic soils worldwide are regularly subjected to high SIC applications in the form of lime to remediate acidity, which is another direct source of CO2 emission. Consequently, global efforts to mitigate climate change through SOC sequestration need a revisit as SIC-borne C losses are significant both in terms of C stocks and soil fertility loss, upon which future SOC sequestration will be reduced. Compared to SOC, wherein C stocks can be increased through management, SIC losses are irreversible and cause significant decline in soil health, ecosystem services, and functions. The present review is the first to summarize the current information about acidification-induced intensified SIC losses and their mechanisms. It included: (i) natural and anthropogenic sources and causes of soil acidification, (ii) losses of SIC as HCO3− leaching and CO2 efflux from calcareous soils (7.5 Tg C yr−1) and liming (273 Tg C yr−1) during acidity neutralization, (iii) the relationship between climate change and SIC stocks, (iv) consequences of SIC depletion in soil-plant-water systems, and (v) strategies to remediate and control soil acidification. We concluded that acidification-induced SIC-borne CO2 losses are a major C loss pathway and could jeopardize global efforts to mitigate climate change through SOC sequestration. © 2021 Elsevier Ltd