It is increasingly recognized that uncertainty concerns more than statistical errors and incomplete information. Uncertainty becomes particularly important in decision-making when it influences the ability of the decision-makers to understand or solve a problem. While the literature on uncertainty and the way in which uncertainty in decision-making is conceptualized continue to evolve, the many uncertainties encountered in policy development and projects are still mostly represented as individual and separated issues. In this paper, we explore the relationship between fundamentally different uncertainties – which could be classified as unpredictability, incomplete knowledge or ambiguity – and show that uncertainties are not isolated. Based on two case studies of ecological engineering flood defence projects, we demonstrate that important ambiguities are directly related to unpredictability and incomplete knowledge in cascades of interrelated uncertainties. We argue that conceptualizing uncertainties as cascades provides new opportunities for coping with uncertainty. As the uncertainties throughout the cascade are interrelated, this suggests that coping with a particular uncertainty in the cascade will influence others related to it. Each uncertainty in a cascade is a potential node of intervention or facilitation. Thus, if a particular coping strategy fails or system conditions change, the cascades point at new directions for coping with the uncertainties encountered. Furthermore, the cascades can function as an instrument to bridge the gap between actors from science and policy, as it explicitly shows that uncertainties held relevant in different arenas are actually directly related.