An array of magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy experiments is applied to explore the surface reactions of a mesoporous bioactive glass (MBG) of composition Ca_0.10Si_0.85P_0.04O_1.90 when subjected to a simulated body fluid (SBF) for variable intervals. Powder X-ray diffraction and ³¹P NMR techniques are employed to quantitatively monitor the formation of an initially amorphous calcium phosphate surface layer and its subsequent crystallization into hydroxycarbonate apatite (HCA). Prior to the onset of HCA formation, ¹H → ²⁹Si cross-polarization (CP) NMR evidence dissolution of calcium ions; a slightly increased connectivity of the speciation of silicate ions is observed at the MBG surface over 1 week of SBF exposure. The incorporation of carbonate and sodium ions into the bioactive orthophosphate surface layer is explored by ¹H → ¹³C CPMAS and ²³Na NMR, respectively. We discuss similarities and distinctions in composition−bioactivity relationships established for traditional melt-prepared bioglasses compared to MBGs. The high bioactivity of phosphorus-bearing MBGs is rationalized to stem from an acceleration of their surface reactions due to presence of amorphous calcium orthophosphate clusters of the MBG pore wall.