The El Niño/Southern Oscillation (ENSO) is the leading mode of tropical Pacific interannual variability in the present-day climate. Available proxy evidence suggests that ENSO also existed during past climates, for example during the Pliocene extending from about 5.3 million to about 2.6 million years BP. Here we investigate the influences of the Panama Seaway closing and Indonesian Passages narrowing, and also of atmospheric carbon dioxide (CO2) on the tropical Pacific mean climate and annual cycle, and their combined impact on ENSO during the Pliocene. To this end the Kiel Climate Model), a global climate model, is employed to study the influences of the changing geometry and CO2-concentration. We find that ENSO is sensitive to the closing of the Panama Seaway, with ENSO amplitude being reduced by about 15–20 %. The narrowing of the Indonesian Passages enhances ENSO strength but only by about 6 %. ENSO period changes are modest and the spectral ENSO peak stays rather broad. Annual cycle changes are more prominent. An intensification of the annual cycle by about 50 % is simulated in response to the closing of the Panama Seaway, which is largely attributed to the strengthening of meridional wind stress. In comparison to the closing of the Panama Seaway, the narrowing of the Indonesian Passages only drives relatively weak changes in the annual cycle. A robust relationship is found such that ENSO amplitude strengthens when the annual cycle amplitude weakens.