For the purpose of uncovering the influence law on the explosion stress wave transmission and blast-induced crack propagation by inclined natural fracture and water jet slot, the influential mechanism for the transmission law of explosion stress wave due to inclined natural fracture was analyzed based on stress wave theory in this article. Next, the evolution law of explosion stress wave and blast-induced crack propagation affected by inclined natural fracture and water jet slot were simulated by ANSYS/LS-DYNA, and an experiment was conducted to understand the crack propagation law under explosion shock wave loading. The results indicate that the existence of inclined natural fracture will affect the “guiding effect” of water jet slot on blast-induced crack propagation by changing the propagation path and mechanical properties of the explosion stress wave. When the distance between inclined natural fracture and blast hole is too small, the water jet slot cannot play a guiding role in propagation process of blast-induced main crack. With the increase of the distance, the propagation direction of blast-induced crack is affected by both inclined natural fracture and water jet slot. When the distance increases further and exceeds a certain value, inclined natural fracture cannot affect the guiding effect of water jet slot in propagation process of blast-induced main crack.