Lower crustal earthquakes are commonly observed in continental rifts at depths where temperatures should be too high for brittle failure to occur. Here we present accurately located earthquakes in central Ethiopia, covering an incipient oceanic plate boundary in the Main Ethiopian Rift. Seismicity is evaluated using the combination of exceptionally well resolved seismic structure of the crust and upper mantle, electromagnetic properties of the crust, rock geochemistry, and geological data. The combined data sets provide evidence that lower crustal earthquakes are focused in mafic lower crust containing pockets of the largest fraction of partial melt. The pattern of seismicity and distribution of crustal melt also correlates closely with presence of partial melt in the upper mantle, suggesting lower crustal earthquakes are induced by ongoing crustal modification through magma emplacement that is driven by partial melting of the mantle. Our results show that magmatic processes control not only the distribution of shallow seismicity and volcanic activity along the axis of the rift valley but also anomalous earthquakes in the lower crust away from these zones of localized strain.