The sliding movement between oceanic and crustal plates in subduction zones is accommodated through both earthquakes and quasi-static or transient aseismic slip. On northeastern Japan megathrust, aseismic transients, known as slow-slip events, are suggested to precede and trigger major earthquakes in their immediate surroundings. However, the geodetic evidence for these episodic slow-slip events, as well as their link to the seismicity on neighboring locked segments of the megathrust, is missing. Here, we combine the on-shore geodetic data set with seismic observations during the interseismic period of 1996–2003 and demonstrate that episodic slow-slip events are prevalent across the down-dip portion (∼30–70 km depth) of the megathrust and the associated stress changes modulate the seismicity rate on the neighboring seismogenic zone. Consequently, small- to moderate-size earthquakes are periodically triggered, whose interaction through a domino effect might occasionally lead to major earthquakes. This observation has a profound impact on the estimation of seismic hazard in the region, introducing a new triggering mechanism that acts across the megathrust to the extent that has not been acknowledged before.