Coral reef karstification plays a vital role in sea-air CO2 exchange, yet its mechanisms remain unclear. This study employs an 878.22-m coral reef sequence (dating to19.6 Ma) from Well CK2 in the Xisha Islands, South China Sea (SCS), to investigate karstification processes, including their signatures, primary controls, and implications for marine carbonate dissolution in global carbon cycling. Petrological and geochemical analyses of CK2 revel distinct karstification characteristics, including: (1) higher surface porosity 25-30%), with randomly distributed pores and fractures of variable sizes and shapes; (2) yellowish-brown to black impregnations; (3) micritic cements accompanied by well-crystallized mineral crystals, and (4) moderately well-sorted and rounded grains. Geochemical signatures show elevated 8787Sr/86Sr, Mn content, and Mn/Sr ratios, coupled with depleted delta C-1(3), delta 18O and Sr content. These features collectively indicate that karstification in CK2 was dominated by non-selective dissolution and recrystallization processes, principally occurring at the mixing zone in meteoric water systems during prolonged subaerial exposure. Karstification signatures varied across geological epochs, implying different controlling mechanisms. Late Miocene (12.6-10.2 Ma), driven by sustained sea-level fall, exhibited an extreme 87Sr/86Sr shift and severe erosion. Pleistocene (2.2-1.8, 1.1-0.89, 0.29 and 0.2 Ma), influenced by frequent sea-level fluctuations and warm, humid environments linked to glacial-interglacial cycle and Asian monsoon, displayed the highest surface porosity (15-40%, mean 25%), ochre to tawny impregnations, and micritized cements, along with negative delta C-1(3)-delta 18O and elevated 87Sr/86Sr and Mn/Sr ratios. In contrast, the Middle Miocene Climatic Optimum (16.6-16 Ma) lacked typical karst characteristics but comprised of well-rounded and sorted coral gravels, suggesting reef-building organisms mediate karstification via substrate architecture. These findings demonstrate that sea-level changes and climate conditions control coral reef karstification intensity. Concurrently, dissolution during karstification may significantly modify ocean alkalinity and dissolved inorganic carbon, with potential feedback on carbon cycling in future climate scenarios.