To investigate the physical mechanism of fracture activation induced by fluid injection, a series of triaxial injection-driven shear experiments were performed on sandstone cylindrical samples with a single fracture. The slipping conditions and modes of fracture activated by the fluid injection were analyzed. The results show that the initiation of fracture slippage largely depends on the stress state and the roughness characteristics of the fracture surface. Fluid pressure is the main cause of fracture slippage, while the degree of the nonuniform distribution of fluid pressure and the evolution permeability are the secondary causes. The fluid pressurization rate regulates the slipping mode of fracture. While the roughness characteristics of the fracture surface and permeability evolution characteristics are positively correlated with the rate of fracture slippage, they are negatively correlated with the rate of fluid pressurization. Under laboratory conditions, effective normal stress ＞20 MPa and Coulomb rupture stress ＞1.6 MPa will pose a serious threat to fracture stability, which is significant for evaluating the instability of natural faults activated by fluid injection.