The paper characterizes concurrent effects of gamma-irradiation and presence of water in Portland cement pastes. An extensive nanomechanical quantification (Young’s modulus, hardness, and creep compliance) at two scales is performed after exposure to two gamma-ray doses and a wide range of relative humidities (RH 0%–100%). Competing microstructural mechanisms such as water radiolysis, hydration, carbonation and drying were identified and their effects de-coupled with the aid of nanoindentation and other supporting techniques. Maximum radiation resistance was found for samples in medium humidities (33%–57%). Samples irradiated below 11% RH exhibited compaction of C-S-H phases at the level of 100 nm, ∼25% increase of Young’s modulus and decrease of creep compliance due to water radiolysis and drying. The compaction resulted in microcracking at higher paste scale and caused ∼17% decrease of elastic modulus. Samples irradiated in water showed large (∼26%) decrease of Young’s modulus and increased creep compliance accompanied by 9%–10% Portlandite loss.