Author summary Dengue fever is a dramatically expanding disease transmitted by mosquitoes. Earlier research has demonstrated the susceptibility of dengue-carrying mosquitoes to weather conditions, with rainfall and temperature significantly impacting dengue transmission. While there is evidence of a connection between weather factors, the El Niño-Southern Oscillation (ENSO) and the risk of dengue, their impact on the behaviour of Aedes (Ae.) aegypti mosquitoes, which is the main disease vectors, remains poorly comprehended. In this study we analyse municipality-specific time series of a larval index of Ae. aegypti population in the State of São Paulo (southern Brazil) from 2008 to 2018. The main goal was to explore how intra- and inter-annual changes in weather conditions and ENSO periodic fluctuations affected mosquito abundance. We found a strong and significant coherence between the temporal pattern of mosquito abundance and El Niño phases, rainfall and temperature, showing the role that climate plays in driving infestation periodicity. Specifically, we identified a relationship between Ae. aegypti infestation and the strength of the ENSO phenomenon: periods characterized by El Niño phase (moderate to strong) were associated with a higher abundance of Ae. aegypti mosquito larvae. Additionally, we found that wealth inequalities increase opportunities for Ae. aegypti proliferation. Our discoveries carry significant implications for vector control strategies, as they offer valuable insights for categorizing areas based on spatial risk, enabling the prioritization of intensified vector control measures. Given the anticipated rise in the frequency of El Niño events due to climate change, these findings suggest that arbovirus outbreaks could also see an increase, and that El Niño occurrences might serve as a predictive tool for such outbreaks.