An evaporite varve thickness record from the Late Miocene Mediterranean reveals significant signals of interannual variability, the frequency and persistence of which are compared with climatic oscillations affecting the region today. Sustained variability in the 2–7 yr band resembles the modern spectrum of the El Niño Southern Oscillation (ENSO) and contrasts with that of the North Atlantic Oscillation (NAO), the cyclicity of which is less stationary in frequency and less sustained in duration. Fully coupled climate model simulations demonstrate not only that ENSO variability persisted during the Late Miocene, but also that its teleconnections may have extended further than today, as high-latitude climate modes weakened due to a reduced meridional temperature gradient. ENSO appears to have exerted a stronger influence on the evaporative balance of the Mediterranean in the Late Miocene than it does today. This evidence suggests that the Pacific prior to the Northern Hemisphere glaciation was characterized by ongoing interannual variability.