Bioactive glasses (BGs) have been applied for bone transplant surgery, dentistry, and drug delivery due to their high reactive surface areas and excellent bioactive properties. Spray pyrolysis (SP) has been employed to fabricate BG in order to overcome the disadvantages of common techniques such as the conventional glass method (low purity and high calcination temperature) and the sol-gel method (difficulties in mass production). Bioactivity, the most important property of BGs, is directly related to surface area. It is well known that BG surface area increases greatly with decreasing particle size. Therefore, in this study, both submicron and nanostructured BG particles were synthesized in order to determine the effect of particle size on bioactivity by adjusting the SP calcination temperature. The surface structure, morphology, crystallography, chemical composition, and surface area of BG particles were characterized using scanning and transmission electron microscopy, selected area electron diffraction, Fourier transform-infrared spectroscopy, and the Brunauer-Emmett-Teller method. It was found that with increasing calcination temperature, the particle morphology changed from submicron solid structures to nanosized hollow structures. In addition, the surface area increased from 6.0 to 20.1 m2/g. The bioactivity test suggests that nanosized BG particles have a higher hydroxyl apatite formation rate due to their higher surface area. Based on these experimental results, SP formation mechanisms for BGs particles with various morphologies based on the “one-particle-per-drop” and “gas to particle conversion” mechanisms are proposed. By controlling the SP calcination temperature, BG morphologies crystallographic structures and surface areas have been correlated with their bioactivities. These findings demonstrate that SP can be used for BG fabrication.