The quest for safe, orderly and regular migration underpins the UN Global Compact for Migration (GCM) and translates into “comprehensive and integrated” responses to large movements of refugees and migrants. The effort to de-compartmentalise the governance of cross-border human mobility through “comprehensiveness” shapes the overall search for greater policy coherence via regime interaction and shared responsibility within the GCM. A similar effort has been made at the EU level to overcome the “silos approach” characterising the distinct policies on migration, asylum, and border management. This parallelism is particularly meaningful as the reason is twofold: at the operational level, because of the role played by the EU in fashioning the cooperation models underpinning the GCM, which enhances the relevance of EU law and practice for the implementation of the GCM; at the normative level, because the GCM draws on four guiding principles—i.e., sovereignty, good governance, human-centricity, and the rule of law—which are also key features of the EU legal system. Departing from these premises, this article reveals the meaning of “comprehensive and integrated” responses to large movements of refugees and migrants in the GCM and EU border policies. It does so in order to provide a critical appraisal of the legal and policy implications of comprehensive approaches in the global and European governance of cross-border human mobility.