Large changes in seawater chemistry accompanied a decline in atmospheric CO (sub 2) and cooling of Earth's climate over the Cenozoic. Sources and sinks of magnesium in seawater have distinct isotopic compositions, making the magnesium isotopic composition of seawater a tracer of the processes that control seawater chemistry. Here we present Mg isotope data from both pore-fluids and pelagic carbonate sediments from ODP sites 1265 and 807A in the Atlantic and Pacific ocean basins, resepecitvely. Pore-fluid profiles of Mg and Ca in deep-sea carbonate sediments can be explained to first order by the recrystallization of biogenic carbonate and changes in Cenozoic seawater Mg and Ca. Our results are consistent with a substantial (>10 mmol) increase in seawater Mg over the Neogene, approximately balanced by a similar decline in seawater Ca. Magnesium isotope ratios measured in pelagic carbonates and corrected for re-crystallization vary systematically: peaking in the Paleogene, declining by approximately 0.4 ppm to the Oligocene-Miocene boundary and remaining approximately constant from the Miocene to the present. Using a numerical model of global geochemical cycles (C, Mg, Ca, alkalinity), we explore mechanisms for changing seawater Mg and Ca and discuss implications for carbon cycling during the Neogene.