Climate change has a strong influence on weather patterns and significantly affects crop yields globally. El Niño Southern Oscillation (ENSO) has a strong influence on the U.S. climate and is related to agricultural production variability. ENSO effects are location-specific and in southeastern U.S. strongly connect with climate variability. When combined with climate change, the effects on growing season climate patterns and crop yields might be greater than expected. In our study, historical monthly precipitation and temperature data were coupled with non-irrigated maize yield data (33-43 years depending on the location) to show a potential yield suppression of ~15% for one °C increase in southeastern U.S. growing season maximum temperature. Yield suppression ranged between -25 and -2% among locations suppressing the southeastern U.S. average yield trend since 1981 by 17 kg ha(-1)year(-1) (~25%), mainly due to year-to-year June temperature anomalies. Yields varied among ENSO phases from 1971-2013, with greater yields observed during El Niño phase. During La Niña years, maximum June temperatures were higher than Neutral and El Niño, whereas June precipitation was lower than El Niño years. Our data highlight the importance of developing location-specific adaptation strategies quantifying both, climate change and ENSO effects on month-specific growing season climate conditions.