The dissolution behavior of Pyrex glass in a model system consisting of 1-M NaOH with varying amounts of portlandite, representing the glass dissolution in alkaline environment and alkali-silica reaction (ASR) in cementitious materials, is studied. The Pyrex glass dissolution and the reaction products were characterized using X-ray diffraction (XRD), Si-29 nuclear magnetic resonance (Si-29-NMR), and scanning electron microscopy with energy dispersive X-ray (SEM/EDX), and the silica and calcium concentrations in the liquid phase were determined using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The experimental results show that the dissolution of the Pyrex glass continued until it consumed the portlandite and then reached a constant rate, with a linear relationship with the amount of portlandite. The absence of calcium and reduction of silica concentration in the liquid phase with the increase in portlandite indicate the formation of high-reaction products with portlandite, confirmed by XRD and Si-29-NMR. The calcium sodium silicate hydrate (C-N-S-H) and sodium silicate hydrate (N-S-H) are the main ASR products; their composition and proportions strongly depend on the reaction time and the amount of portlandite added. A thermodynamic model, which couples geochemical code (PHREEQC) and the experimental silica dissolution rate, was used to predict ASR products and the remaining portlandite. The simulation results predicted the experimental data fairly well for different portlandite additions. The mechanism for Pyrex glass dissolution in the presence of varying portlandite additions is discussed with regard to experimental data and simulation results.