The ratio of monthly median f_oF₂ values between the ionosondes at Maui (20.8°N, −156°E geographic; 21.2°N, −90.4°E geomagnetic) and Yamagawa (31.2°N, 130.6°E geographic; 20.6°N, −160.9°E geomagnetic) from January 1960 to June 1993 are used to investigate interannual variability in the wave-4 longitudinal structure of the low-latitude F region ionosphere. Analysis of Global Positioning System total electron content between January 1998 and December 2008 reveals that the ratio between these two locations is a suitable proxy for the amplitude of the wave-4 longitudinal structure in the Northern Hemisphere. Significant interannual variability is present in the f_oF₂ ratio after removing the solar cycle and intra-annual variability. The remaining variability is thought to be due, in part, to changes in atmospheric and oceanic circulations arising from the El Niño–Southern Oscillation (ENSO). Wavelet analysis reveals that similar periodicities and occurrence times exist for the f_oF₂ ratio monthly anomalies and sea surface temperature anomalies, represented by the Oceanic Niño Index (ONI). Furthermore, the yearly ONI extreme value is well correlated with the extreme value of the f_oF₂ ratio monthly anomalies in the subsequent 5 months. This surprising connection is attributed to changes in tropospheric convection, and hence latent heating, associated with changing sea surface temperatures due to the ENSO. Changing distributions of latent heat tidal forcing are thought to induce changes in the strength of the upward and eastward propagating diurnal tide with zonal wave number s = −3 (DE3) which subsequently produces the observed changes in the amplitude of the wave-4 longitudinal structure through modulation of the electric fields generated by the dynamo mechanism in the ionospheric E region. Our results demonstrate that there is significant interannual variability in the ionospheric wave-4 longitudinal structure and further indicate that the ENSO phenomenon represents a source of ionospheric variability which has previously not been considered.