Background The emergence of Zika virus (ZIKV) as a public health emergency in Latin America and the Caribbean (LAC) occurred during a period of severe drought and unusually high temperatures. Speculation in the literature exists that these climate conditions were associated with the 2015/2016 El Nino event and/or climate change but to date no quantitative assessment has been made. Analysis of related flaviviruses -such as dengue and chikungunya, which are transmitted by the same vectors- suggests that ZIKV dynamics is sensitive to climate seasonality and longer-term variability and trends. A better understanding the climate conditions conducive to the 2014-2016 epidemic may permit the development of climate-informed short- and long-term strategies for ZIKV prevention and control. Results Using a novel timescale-decomposition methodology, we demonstrate that extreme climate anomalies observed in most parts of South America during the current epidemic are not caused exclusively by El Nino or climate change -as speculated-, but are the result of a particular combination of climate signals acting at multiple timescales. In Brazil, the heart of the epidemic, we find that dry conditions present during 2013-2015 are explained primarily by year-to-year variability superimposed on decadal variability, but with little contribution of long-term trends. In contrast, the extreme warm temperatures of 2014-2015 resulted from the compound effect of climate change, decadal and year-to-year climate variability. Conclusions ZIKV response strategies adapted for a drought context in Brazil during El Nino 2015/2016 may need to be revised to accommodate the likely return of heavy rainfall associated with the probable 2016/2017 La Nina. Temperatures are likely to remain warm given the importance of long term and decadal scale climate signals.