Malaria is a complex multi-factorial disease whose outcomes are affected by climate and environmental variability. In particular, malaria is endemic in the year-round hot and humid lowlands of Colombia, whose hydro-climatology exhibits clear-cut variability at interannual timescales, mostly driven by both phases of El Nino/Southern Oscillation (ENSO): El Nino (warm phase) and La Nina (cold phase). Here we show highly significant statistical correlations between malaria outbreaks in Colombia during historical El Nino events of 1959-2009. Analyses are performed at national, regional, and municipal spatial scales, and at annual, quarterly, and monthly timescales. Annual malaria incidence in Colombia exhibits a combination of long-term trends (which might be explained by historical increasing trends in average air temperatures throughout Colombia, in turn owing to global warming and deforestation), as well as strong malaria outbreaks during El Nino, as a consequence of the concomitant increases in air temperature. Also, we show that satellite imagery of vegetation activity can be used as an environmental indicator for malaria in Colombia. We discuss how these research results and diverse knowledge-based tools, including mathematical explanatory models and geographical information systems, are being used by the Colombian health authorities as an end-to-end program and early warning system (EWS) for malaria prevention and surveillance countrywide.