Extensive microdiversity within Prochlorococcus, the most abundant marine cyanobacterium, occurs at scales from a single droplet of seawater to ocean basins. To interpret the structuring role of variations in genetic potential, as well as metabolic and physiological acclimation, we developed a mechanistic constraint-based modeling framework that incorporates the full suite of genes, proteins, metabolic reactions, pigments, and biochemical compositions of 69 sequenced isolates spanning the Prochlorococcus pangenome. Optimizing each strain to the local, observed physical and chemical environment along an Atlantic Ocean transect, we predicted variations in strain-specific patterns of growth rate, metabolic configuration, and physiological state, defining subtle niche subspaces directly attributable to differences in their encoded metabolic potential. Predicted growth rates covaried with observed ecotype abundances, affirming their significance as a measure of fitness and inferring a nonlinear density dependence of mortality. Our study demonstrates the potential to interpret global-scale ecosystem organization in terms of cellular-scale processes.