Southeast Asia, an important region of the “21st-Century Maritime Silk Road”, has been struck by more than ten giant devastating earthquakes historically. Accordingly, the earthquakes and associated geological hazards are the main natural hazards threatening the socio-economic development and international cooperation in this region. Systematic investigation on spatiotemporal distribution of the seismicity and the assessment of the future earthquake hazard risk hold key for advancing the“the Belt and Road”Initiative and socio-economic sustainable development in the region. Based on the analysis of the spatiotemporal distribution of Magnitude≥5 earthquakes in Southeast Asia since 1900 and the calculation of regional seismic b-values, our results show that the seismicity in Southeast Asia is featured by the alternations of active and quiescent periods temporally. The seismicity also demonstrates a spatially strong clustering, mainly concentrating on five seismic sub-areas. Among which the Indonesia-Malay archipelagic area and the Philippine islands show intensive earthquake activities. Generally the seismic b-values for this region are low, ranging between 0.42 and 0.91, but show an obviously spatiotemporal variation as well. Seismic b-value of Southeast Asia is mainly affected by the factors that include the large earthquake events, the age of subduction zones, the active fault zone and the focal depth, but their relative contributions are various for different areas. The spatiotemporal variation of seismic b-value is of significance for regional earthquake prediction. The results could provide some scientific supports for reinforcing engineering infrastructures of the Maritime Silk Road and the mitigation of the earthquake hazards for the commencement of the Belt and Road Initiative.