The effects of carboxylated multi-walled carbon nanotubes (MWCNTs) are studied experimentally and theoretically on mixed-mode (I/II) fracture behavior of epoxy resin at the presence of hygrothermal aging conditions. In this paper, the mixed-mode fracture of MWCNT/epoxy is experimentally measured using Short Beam Bending (SBB) samples with different crack inclination angles (α) ranging from pure mode I (i.e., α = 0°) to pure mode II (i.e., α = 39°). To examine the effects of hygrothermal aging conditions and water barrier properties of MWCNTs, four groups of samples including a group of neat epoxy specimens, and three groups of MWCNT/epoxy specimens (with 0.1, 0.3, and 0.5 wt% of MWCNTs) were manufactured and immersed into hot deionized water for 15 days at 60 °C temperature and similarly four groups were placed at room temperature conditions (26 °C and 25–35% relative humidity) for 15 days. According to the experimental results, toughening the epoxy resin by incorporating nanotubes with 0.1, 0.3, and 0.5 wt% of MWCNTs improved the fracture toughness at both environmental conditions, but the highest fracture toughness was obtained for composition containing 0.3 wt% nanoparticles. The variations of fracture loads were dependent on the ambient environment, MWCNTs content, and mode mixity. The relationship between the obtained experimental results, microstructure and morphology of fracture in the tested samples was also investigated. In addition, the load-carrying capacity of the SBB samples made of the neat and MWCNTs modified epoxy material was also predicted well using a two-term based fracture model called Generalized Maximum Tangential Stress (GMTS) criterion.