Calcium aluminosilicate (CAS) glasses are the main reactive component in supplementary cementitious materials such as fly ashes and slags, which may also include significant amounts of magnesium. Eighteen CAS glasses have been synthesized in six series with 0, 25, and 50 mol% of Ca substituted by Mg. Their structure, pozzolanic reactivity and impact on Portland cement hydration are investigated by ²⁹Si and ²⁷Al NMR spectroscopy and TGA analysis. The aluminosilicate network is only slightly affected by the Mg for Ca substitution, although an increased distortion of the network is observed, which is ascribed to a lowering of the Mg coordination state relative to Ca. The glass reactivity is mainly governed by the network depolymerization, which increases with the MgO + CaO content, with Mg substitution only having a minor impact. Increasing Mg contents in the glasses lead to OH-hydrotalcite formation and a smaller fraction of Al incorporated in the C-A-S-H phase.