Abstract Rare earth element concentrations, ϵ Nd ( T) values, and strontium isotopic compositions of mollusc shells were used to trace variations in the neodymium and strontium isotopic composition of the epicontinental Late Cretaceous Western Interior seaway of North America. Rare earth element patterns are different in aragonite and calcite produced by the molluscs endemic to the seaway, indicating that either mineralogical control or possibly scavenging by organic films associated with the different phases of biogenic carbonate resulted in differential partitioning of the REEs from seawater during shell formation. The biogenic carbonate also may contain REEs associated with Fe-flocs trapped in the shells during growth, but these flocs cannot result in different REE patterns of aragonite and calcite produced by the molluscs. The neodymium isotopic composition of the Western Interior seaway is inferred to have varied 13 ϵ-units over 20 My as a result of incursions of seawater from the Arctic Ocean and Gulf of Mexico, river influx from tectonically active terranes, benthic diagenetic fluxes, and volcanic ash falls. Ash from a variety of volcanic centers in western North America was significant in producing rapid and marked changes in 143Nd 144Nd ratios of the seaway, and abrupt regional variations in neodymium isotopic composition of the seaway make the construction of an accurate neodymium isotope evolution curve difficult for this basin. Strontium isotopic compositions of the mollusc shells indicate the 87Sr 86Sr ratio of the Western Interior seaway was generally similar to contemporaneous oceans, although, periodically, the basin had strontium isotopic compositions distinct from contemporaneous seawater. An ϵ Nd ( T) value of +6.2 is recorded in a molluscan shell from the Cenomanian-Turonian boundary interval, which is a time associated with a global anoxic event, biotic crisis, and elevated Ir contents in sedimentary rocks. Neither a marked Ce anomaly nor a significant variation in Th U ratios is observed in the mollusc shell for this time, nor are Ce anomalies or aberrant Th U ratios evident in mollusc shells correlative with other periods of low oxygenation of the Western Interior seaway. The high ϵ Nd ( T) value near the Cenomanian-Turonian boundary may imply a terrestrial source for the anomalous Ir contents in strata of this age in the Western Interior Basin.