Carbon fiber reinforced polymer (CFRP) multidirectional composite laminates are vital for moisture-prone structures where directional fatigue properties can be optimized. In this work, the tension-tension(T-T) and tension-compression(T-C) fatigue properties of hygrothermal aged [±454]S and [+45,−45, 0, 90]2S laminates were compared with virgin properties. The effect of fiber orientation and hygrothermal aging on moisture diffusivity, FTIR spectra, glass transition temperature, and static strength was also investigated. The fiber orientation had a minor impact on moisture diffusivity, static strength, and fatigue strength. Aging caused degradation in T-C fatigue life was higher as compared to T-T loading due to fiber-matrix debonding and matrix properties deterioration.