Metal (M) oxides are one of the most interesting and widely used solids, and many of their properties can be directly correlated to the local structural ordering within basic building units (BBUs). One particular example is the high-Ni transition metal layered oxides, potential cathode materials for Li-ion batteries whose electrochemical activity is largely determined by the cationic ordering in octahedra (e.g., the BBUs in such systems). Yet to be firmly established is how the BBUs are inherited from precursors and subsequently evolve into the desired ordering during synthesis. Herein, a multimodal in situ X-ray characterization approach is employed to investigate the synthesis process in preparing Li-Ni0.77Mn0.13Co0.10O2 from its hydroxide counterpart, at scales varying from the long-range to local individual octahedral units. Real-time observation corroborated by first-principles calculations reveals a topotactic transformation throughout the entire process, during which the layered framework is retained; however, due to preferential oxidation of Co and Mn over Ni, significant changes happen locally within NiO6 octahedra. Specifically, oxygen loss and the associated symmetry breaking occur in NiO6; as a consequence, Ni2+ ions become highly mobile and tend to mix with Li, causing high cationic disordering upon formation of the layered oxides. Only through high-temperature heat treatment, Ni is further oxidized, thereby inducing symmetry reconstruction and, concomitantly, cationic ordering within NiO6 octahedra. Findings from this study shed light on designing high-Ni layered oxide cathodes and, more broadly, various functional materials through synthetic control of the constituent BBUs.