Many hydraulic fracturing experiments suggest that low-viscosity fluid tends to generate a complex fracture network, which may be beneficial for geo-energy production. However, the precise impacts of low-viscosity fluid on the fracture nucleation and propagation are unknown. This study focuses on the stress jump at weak interfaces (e.g., grain boundaries or natural fractures) caused by the contrast in Biot’s coefficient, which is prevalent in hard rocks, and how failure may develop. We found that fracture nucleation at weak interfaces becomes favorable under certain Biot’s coefficient contrast and fluid viscosity. Our numerical simulations of fluid injection through a borehole demonstrate that low-viscosity fluid injection can nucleate isolated fractures at remote interfaces without connecting to the main propagating fracture. These findings imply the necessity to consider Biot’s coefficient variations within a rock mass in applications such as hydraulic fracturing or induced seismicity, especially when a diffused pressure gradient persists due to the low-viscosity fluid.