Amorphous calcium orthophosphates (ACP) are bioactive compounds presenting high interest as bone substitute. However, the synthesis of such metastable products requires special attention as they can rapidly evolve into a crystalline phase during the elaboration process. The resulting increased stability generally leads to less bioactive reactive materials. Among the various strategies developed to obtain stable form of ACP, the use of spray drying is an effective and reproducible route. Compared to previous works, this study aims to demonstrate for the first time the feasibility of ACP elaboration by spray drying directly from a single solution of selected precursors. Moreover, structuration of the spray-dried powders was determined at different length scales, demonstrating a hierarchical organization from nanometric clusters to particles aggregates. These complementary analyses highlighted a thorough mechanism of particles formation during processing. The effect of the initial composition of the solution was observed, and it was demonstrated that there is a correlation with the purity of the final product that may be modulated. In addition, ACP powders were found to be highly reactive in aqueous medium and their fast transformation into low crystalline apatite suggests a good suitability for biomedical use.