The changes in structural integrity and microstructure of Portland-limestone cement pastes were investigated in the course of magnesium sulfate attack at low temperature. A deterioration front, consisting of three distinct layers (brucite, gypsum, leached cement matrix), swelled in time due to the expansive nature of the deterioration products, generating cracks and subsequently detaching from the sound cement matrix, continuously promoting the process. Gypsum and thaumasite characterized the leached matrix, which experienced extensive cross-linking of the aluminosilicate structures, as a result of decalcification and dealumination of the calcium silicate hydrates (C-(A-)S-H), impairing the overall mechanical performance. C-S-H of low packing density was most severely affected by the process, as confirmed by the significant drop in nano-mechanical properties. The increased rate of deterioration with limestone content was tentatively attributed to the prevalent morphology of the C-S-H phase. Results were validated by thermodynamic simulations, indicating that the real systems did not reach equilibrium.