Fluid overpressure and fluid migration are known to be able to trigger or induce fault slip. However, relatively little is known about the role of fluids on generating earthquakes in some of the major continental rifts. To address this, we investigate the interaction between fluids and faults in the Main Ethiopian Rift (MER) using a large seismicity catalog that covers both the rift axis and rift margin. We performed cross-correlation analysis on four major earthquake clusters (three within the rift and one on the rift margin) in order to significantly improve accuracy of the earthquake relative relocations and to quantify families of earthquakes in which waveforms are similar. We also analyzed variation of seismicity rate and seismic moment release through time for the four clusters. The major results are that for all four clusters the earthquake relocations are 5–15 km deep, aligned to clear N-NNE striking, steeply (>60°) dipping planes. For the three clusters within the rift, the cross-correlation analysis identifies earthquake families that occur in short swarms during which seismic rate and moment release increases. Together, this space and time pattern of the seismicity strongly points toward them being fluid induced, with fluid likely sourced from depth such as mantle derived CO2. In contrast, the seismicity on the rift margin lacks earthquake families, with occurrence of earthquakes more continuous in nature, which we interpret as pointing toward tectonic stress-driven microseismic creep. Overall, our results suggest that deep sourced fluid migration within the rift is an important driver of earthquake activity