Nutrient supply regulates the activity of phytoplankton, but the global biogeography of nutrient limitation and co-limitation is poorly understood. Prochlorococcus adapt to local environments by gene gains and losses, and we used genomic changes as an indicator of adaptation to nutrient stress. We collected metagenomes from all major ocean regions as part of the Global Ocean Ship-based Hydrographic Investigations Program (Bio-GO-SHIP) and quantified shifts in genes involved in nitrogen, phosphorus, and iron assimilation. We found regional transitions in stress type and severity as well as widespread co-stress. Prochlorococcus stress genes, bottle experiments, and Earth system model predictions were correlated. We propose that the biogeography of multinutrient stress is stoichiometrically linked by controls on nitrogen fixation. Our omics-based description of phytoplankton resource use provides a nuanced and highly resolved description of nutrient stress in the global ocean.