Assessing the risk of complex systems to natural hazards is an important and challenging problem. In today’s intricate socio-technological world, characterized by strong urbanization and technological trends, the connections, interdependencies and interactions between exposed elements are crucial. These complex relations call for a paradigm shift in collective risk assessments, from a reductionist approach to a holistic one. Most commonly, the risk of a system is estimated through a reductionist approach, based on the sum of the risk of its elements individually. In contrast, a holistic approach considers the whole system as a unique entity of interconnected elements, where those connections are taken into account in order to more thoroughly assess risk. To support this paradigm shift, this paper proposes a new holistic approach to assess the risk in complex systems based on Graph Theory. The paper is organized in two parts: part I describes the proposed approach, and part II presents an application to a pilot study in Mexico City. In part I, we demonstrate that by representing a complex system such as an urban settlement by means of a network (i.e. a graph), it is possible to take advantage of the techniques made available by the branch of mathematics called Graph Theory to analyse its properties. Moreover, it is possible to establish analogies between certain graph metrics (e.g. authority, degree, hub values) and risk variables (exposure, vulnerability and resilience). Leveraging these analogies, one can not only obtain a deeper knowledge of the system (structure, weaknesses, etc.), but also understand its risk mechanisms (how the impacts of a single or multiple natural hazards are propagated, where they are exacerbated), and therefore assess the disaster risk of the system as a whole, including second-order impacts and cascade effects.