Regime shifts, i.e., large, persistent, and usually unexpected changes in ecosystems and social-ecological systems, can have major impacts on ecosystem services, and consequently, on human well-being. However, the vulnerability of different regions to various regime shifts is largely unknown because evidence for the existence of regime shifts in different ecosystems and parts of the world is scattered and highly uneven. Furthermore, research tends to focus on individual regime shifts rather than comparisons across regime shifts, limiting the potential for identifying common drivers that could reduce the risk of multiple regime shifts simultaneously. Here, we introduce the Regime Shifts Database, an open-access database that systematically synthesizes information on social-ecological regime shifts across a wide range of systems using a consistent, comparative framework, providing a wide-ranging information resource for environmental planning, assessment, research, and teaching initiatives. The database currently contains 28 generic types of regime shifts and > 300 specific case studies. Each entry provides a literature-based synthesis of the key drivers and feedbacks underlying the regime shift, as well as impacts on ecosystem services and human well-being, and possible management options. Across the 28 regime shifts, climate change and agriculture-related activities are the most prominent among a wide range of drivers. Biodiversity, fisheries, and aquatic ecosystems are particularly widely affected, as are key aspects of human well-being, including livelihoods, food and nutrition, and an array of cultural ecosystem services. We hope that the database will stimulate further research and teaching on regime shifts that can inform policy and practice and ultimately enhance our collective ability to manage and govern large, abrupt, systemic changes in the Anthropocene.