In the process of oilfield production, effective stresses usually increase continuously and act as unequal triaxial stresses on the reservoir. However, most studies on rock stress sensitivity are conducted under conventional triaxial or uniaxial stress conditions, which cannot truly represent the in situ stress environment. In this work, two groups of fractured tight sandstones sampled from northwestern China were tested under true-triaxial stress environments to study the stress sensitivity of mechanical and petrophysical properties. The sandstones are elastically deformed under experimental stress conditions, showing an apparent correlation with fracture angles. The acoustic wave velocity increases linearly with the stresses, and the shear wave velocity is strongly affected by fracture angle and anisotropic effective stresses. The permeabilities decrease exponentially and show significant anisotropy with increasing effective stress, which is less stress sensitive when the fracture strike is parallel to the maximum horizontal principal stress than when it is perpendicular. This work successfully reveals the stress sensitivity of anisotropic permeability, stress-strain behavior, and acoustic wave velocity of fractured tight sandstone during reservoir depletion. The testing results provide an innovative method to accurately measure the anisotropic rock properties, offer new ideas about fractures identification, and have profound significance for exploration and development of tight reservoirs.