The 2011 magnitude (M) 9.0 Tohoku-oki earthquake was followed by seismicity activation in inland areas throughout Japan. An outstanding case is the M6.2 Northern Nagano earthquake, central Japan, occurred 13-h after the megathrust event, approximately 400 km away from its epicenter. The physical processes relating the occurrence of megathrust earthquakes and subsequent activation of relatively large inland earthquakes are not well understood. Here we use waveform data of a dense local seismic network to reveal with an unprecedented resolution the complex mechanisms leading to the occurrence of the M6.2 earthquake. We show that previously undetected small earthquakes initiated along the Nagano earthquake source fault at relatively short times after the Tohoku-oki megathrust earthquake, and the local seismicity continued intermittently until the occurrence of the M6.2 event, being likely ‘modulated’ by the arrival of surface waves from large, remote aftershocks off-shore Tohoku. About 1-h before the Nagano earthquake, there was an acceleration of micro-seismicity migrating towards its hypocenter. Migration speeds indicate potential localized slow-slip, culminating with the occurrence of the large inland earthquake, with fluids playing a seismicity-activation role at a regional scale.