As coastal social-ecological systems (SES) are used for many different purposes and subject to different stressors, they are also among the most vulnerable and change the most rapidly. To achieve resilience, coastal areas require adaptive management based on integrated interdisciplinary approaches, requiring a deep understanding of SES dynamics, i.e. the ecological and social changes that comprise synchronicities and regime shifts. For the purpose of analyzing co-evolution and regime shifts, we propose an original and operational methodology combining (i) a chronosystemic timeline approach and (ii) time series analyses based on indicators from the “Drivers-Pressures-State-Impacts-Responses” framework (14 indicators including population growth, eutrophication status, ecosystem services, management actions and climate change indicators). The methodology was tested on a SES located on the French Mediterranean coast, the Thau lagoon, whose trajectory we studied over a 5-decade period (1970–2018). Our results show that the dynamics of co-evolution and regime shifts of the SES were driven by a succession of interactions between sanitary or ecological crises and management adaptations. During the study period, this typical Mediterranean coastal SES appears to have evolved towards the multiplication of uses, improvement of water quality and more integrative management. Our methodology also highlighted three contrasting periods characterized by stable emerging properties and identified several cause-and-effect relationships, which is rare in historical analyses of SES. These cause-and-effect relationships concern major sanitary and ecological crises that have led to a reorganization of governance mechanisms and to technical remediation actions. Our approach based on long-term trajectories will help identify the conditions required for increasing the resilience of coastal SES and the best management objectives to face new challenges related to global climate change.