Cryptosporidium is a leading cause of diarrheal disease in children and an important contributor to early childhood mortality. The parasite invades intestinal epithelial cells and remodels them extensively including building an elaborate interface structure. How this occurs at the molecular level is largely unknown. Here, we generated a whole-cell spatial proteome of the Cryptosporidium sporozoite using the spatial proteomics technology hyperLOPIT. These data in combination with genetic and cell-biological experimentation enabled the discovery of the Cryptosporidium secreted effector proteome, including a new secretory organelle.