To control the COVID-19 epidemic, the Japanese government and the local governments have repeatedly implemented non-pharmaceutical interventions (NPIs) throughout 2020-2022. Using Bayesian state-space mediation models, we examined the effect of repeated NPIs on infection spread mitigation, mediated by human mobility changes in each prefecture during three epidemic phases: from April 1, 2020 to February 28, 2021; from March 1, 2021 to December 16, 2021; and from December 17, 2021 to December 31, 2022. In the first phase, controlling downtown populations at nighttime was effective in mitigating the infection spread in almost all prefectures. In the second and third phases, the effect was not clear, especially in metropolitan prefectures. Controlling visitors from the central prefectures of metropolitan areas was effective in mitigating infection spread in the surrounding prefectures during all phases. These results suggest that the local spread of infection can be mitigated by focusing on nighttime human mobility control in downtown areas before the epidemic spreads widely and transmission routes become more diverse, and that the geospatial spread of infection can be prevented by controlling the flows of people from large cities to other areas.