The spatiotemporal manifestations of seismicity in the Andaman-Sumatra island arc are studied using the instrumental data for 1900–2010. The data on the largest tsunamigenic earthquakes of the 18th–19th centuries were also taken into account. The epicenters of the earthquakes are established to cluster in some areas; their possible relation to the structural features of the island arc is considered. A distinctive feature of seismicity in the region of the Andaman Sea is the presence of compact swarms of numerous earthquakes occurring during short intervals of time. The distribution of the earthquakes by the depth of their hypocenters in different segments of the island arc is investigated. The focal mechanisms of the earthquakes are analyzed using the centroid-moment-tensor (CMT) determinations over the period of 1980–2004, and the characteristic features of their parameters in different segments of the Andaman-Sumatra island arc are formulated. The focal parameters of the earthquakes determined by CMT and the moment-tensor-solution (MTS) are compared; the possible uncertainty in the estimates of the focal mechanisms is assessed. The pattern of the spatiotemporal manifestations of the Andaman-Sumatra earthquakes and their focal mechanisms are compared to the data on the Kuril-Kamchatka and the Aleutian island arcs previously studied by the authors. The results of analyzing the long-term seismicity and focal mechanisms in the Andaman-Sumatra island arc provide a necessary basis for the further thorough investigation of the geological conditions and source parameters of the major Sumatra earthquakes of 2000–2010.