<p>Spherical calcium carbonate (CaCO₃) is widely used as a drug delivery vehicle, food additive, and filler because of its high biocompatibility, biodegradability, and non-toxicity. In particular, the regulation of CaCO₃ particle size enhances the reproducibility of functional properties and plays a critical role in ensuring consistent performance in various applications. However, their size-regulated, morphology-controlled, and eco-friendly preparation remains a challenge. Herein, we report the first successful attempt to provide a promising morphology-controlled fabrication strategy for cellulose nanofiber (CNF)-mediated mesoporous spherical CaCO₃ composite particles with tunable functionality using a scalable, environmentally friendly, 100% aqueous co-spray drying process. Sustainable microfibrillated CNFs with abundant surface hydroxy groups were employed as key 3D structural frameworks for the efficient construction of spherical CaCO₃ composite microparticles. During the spray-drying process, the CNFs facilitated the uniform adhesion of CaCO₃ nanoparticles to the cellulose network through electrostatic interactions. These cohesive interparticle interactions effectively prevented the indiscriminate aggregation of CaCO₃ nanoparticles, resulting in a consistent mesoporous spherical morphology. Furthermore, the morphology and size of the CNF-mediated composite particles were controlled by adjusting the co-spray drying process and material parameters, which influenced the size of the atomized droplets and the solvent evaporation rate during the subsequent drying phase. This green one-pot approach produced multifunctional CNF-mediated composite particles with improved oil and water repellency, high visible and near-infrared reflectance, and superior particle hardness compared to conventional CaCO₃ particles, demonstrating its versatility for the straightforward preparation of sustainable morphology-controllable particles with tunable functionality.</p>