The wide range of gypsum facies observed all over the world and the strong heterogeneity that may be present even within a single facies often cause an inhomogeneous mechanical response that, if neglected, may be particularly dangerous in the framework of underground excavations. In addition, gypsum is particularly sensible to the presence of water. The high relative humidity conditions often registered in underground gypsum quarries may imply an additional worsening of mechanical properties. In the present study, the strength and the creep response of a natural gypsum rock facies are investigated, considering the influence of material heterogeneity and relative humidity conditions. The heterogeneity of the material, quantified with MIP and SEM analyses, is observed to strongly affect the mechanical response. To this intrinsic mechanical variability, the influence of an external parameter as the relative humidity is observed to generate an additional reduction of material strength and to increase the creep strain rate in the long-term tests. The effect of all these elements in the underground quarry framework is discussed and a constitutive model of these experimental results is provided.