Abstract. We develop a novel framework of time-dependent probabilistic tsunami hazard analysis (PTHA) and apply it to Western Sumatra, Indonesia, where future tsunamigenic events are anticipated in the Mentawai region of the Sunda subduction zone. An earthquake rupture model taking into account the spatiotemporal interaction of major megathrust segments is used to simulate future tsunamigenic earthquakes. The earthquake rupture process of the segments is characterized by a multivariate Bernoulli model with interarrival times following a Brownian passage‐time distribution and the dependency between segments specified by a spatial correlation function. We calibrate this model with historical ruptures of the Mentawai thrust in the last 450 years. A total of ≥ 100,000 time-dependent earthquake rupture cases are then coupled with a stochastic tsunami simulation method to evaluate tsunami hazards. We generate a total of 6,300 stochastic tsunami source models from six magnitude scenarios between M 7.75 and M 9.0 and obtain time-dependent PTHA results for seven different periods (1, 5, 10, 20, 30, 50 and 450 years). We further compare the time-dependent PTHA results with a time-independent PTHA approach to investigate the influence of the spatiotemporal earthquake rupture model. The space-time interaction model successfully generates annual seismic moment rates consistent with the observations. Moreover, the model can capture the uncertainty of future time-dependent tsunami hazards. On the other hand, the time-independent approach produces slightly higher hazard estimates than the time-dependent model for long-term hazard assessments (> 450 years).