Here we investigate the fractionation of Mo isotopes (δ98MoNIST) in biogenic carbonates and assess its viability as an environmental and biological proxy in coral skeletons. An annually resolved 40-year record of δ98MoNIST values is reported for a Porites coral from the Great Barrier Reef (GBR), Australia. This, together with a four-day time-series of δ98MoNIST measurements of seawater and samples from a range of coral species from Luhuitou Reef in Sanya Bay, northern South China Sea is used to investigate the relative fractionation of Mo isotopes between coral and seawater and assess the potential of δ98MoNIST as a proxy for tracing biological activity. δ98MoNIST values in the GBR coral skeleton are lighter than those of seawater (2.05‰, relative to NIST SRM 3134) and display large variations from 0.63‰ to 1.73‰, with a mean of 1.29‰. A significant relationship was found between coral δ98MoNIST and sea surface temperature (SSTcal) in the GBR coral. These observations and the Luhuitou Reef seawater data indicate that temperature-mediated biological activity in coral polyps potentially modulate coral δ98MoNIST. A biological fractionation model is proposed to explain how symbiotic zooxanthellae produce the considerable variations in Mo isotopic composition measured in the GBR coral. This fractionation suggests that Mo isotopes could potentially be used as a proxy for biological processes in corals.