Oxygen isotope measurements of seawater (δ18Ow) are an important tool in the study of climate, oceanography, and hydrology, both today and in the past. δ18Ow and salinity are controlled by similar hydrologic processes, but δ18Ow is more readily recorded in geologic materials than salinity and is thus more accessible for paleoceanographic reconstructions. Modern instrumental δ18Ow data exist, but these data can be sparse in certain regions and/or sporadically collected through time - some predating modern instrumentation and current standardization practices. In this dataset, we present 364 new paired salinity and δ18Ow measurements from seawater samples collected along the U.S. Eastern Seaboard, nearly tripling the existing data in this region and dramatically improving spatial coverage. By collecting δ18Ow at such a high spatial resolution, this dataset expands the utility of δ18Ow as a tracer for both modern oceanography and paleoceanography, provides valuable insights into nearshore hydrologic processes and basin-scale ocean dynamics, and offers a robust foundation for more integrated studies of ocean circulation and water-mass properties.