We have developed a coupled ocean-atmosphere general circulation model, the GENESIS-MOM model, with the ability to transport and fractionate water isotopes in the ocean and atmosphere. The model is used to predict modern and Cretaceous precipitation and seawater δ ¹⁸O. The model reproduces the large-scale modern-day isotopic distribution. In the zonal mean, the difference between simulated and observed seawater δ ¹⁸O is within 0.2‰ in the low and middle latitudes and within 1‰ at high latitudes. In comparison to modern, simulated Cretaceous surface seawater δ ¹⁸O is systematically depleted by 0.3‰ at low and middle latitudes. These differences are attributed to equilibrium fractionation during surface evaporation at low latitudes and an increased partitioning of ¹⁸O from the surface into the deep ocean due to intermediate and deep water formation in subtropical basins in the Cretaceous. We also find that regional seawater δ ¹⁸O is significantly influenced by the paleobathymetry and the resolution of oceanic gateways, boundary conditions that are not well known for the past. Our simulation of Cretaceous seawater δ ¹⁸O has major implications for oxygen isotope paleothermometry. We conclude that conventional assumptions of past seawater δ ¹⁸O may lead to an overestimate of Cretaceous sea-surface temperatures, especially at middle and high latitudes.