Apicomplexan parasites cause major human disease and food insecurity. They owe their considerable success to highly specialized cell compartments and structures. These adaptations drive their recognition, nondestructive penetration, and elaborate reengineering of the host’s cells to promote their growth, dissemination, and the countering of host defenses. The evolution of unique apicomplexan cellular compartments is concomitant with vast proteomic novelty. Consequently, half of apicomplexan proteins are unique and uncharacterized. Here, we determine the steady-state subcellular location of thousands of proteins simultaneously within the globally prevalent apicomplexan parasite Toxoplasma gondii. This provides unprecedented comprehensive molecular definition of these unicellular eukaryotes and their specialized compartments, and these data reveal the spatial organizations of protein expression and function, adaptation to hosts, and the underlying evolutionary trajectories of these pathogens. Display omitted •Using hyperLOPIT, Toxoplasma proteins were assigned to their cell location•Complex proteomes associated with host interaction and adaptation are identified•The atlas reveals sites and chronology of cell evolution of apicomplexan parasitism•Cell spatial organization corelates with regulatory and biochemical programs Apicomplexan proteomes are substantially specific to these parasites, and many cellular compartments are highly specialized. Using spatial proteomic methods, Barylyuk et al. simultaneously map the locations of thousands of Toxoplasma proteins, resolving the genomic complexity of this pathogen within the context of its cell organelles, compartments, and structures.