Integrated ecosystem assessment provides a practical framework for implementing ecosystem‐based fisheries management (EBFM) while also balancing socioeconomic and ecological objectives. However, significant challenges remain, including (1) the identification of relevant ecosystem‐level fisheries management indicators; (2) quantitatively describing the historical qualitative changes to fisheries ecosystem resource organization; (3) elucidating dynamic system regimes and their trade‐offs related to variability in both natural and anthropogenic drivers; and (4) distilling and communicating the results to stakeholders and managers. Here, we describe the Ecosystem‐Level, Management‐Indicator Selection Tool (EL‐MIST), which was developed to address these EBFM challenges. We also present a case study from the Gulf of Mexico large marine ecosystem (Gulf LME) where EL‐MIST was applied to 79 time series indicators from the Gulf's 2013 ecosystem status report for the period 1980–2011. Results from Gulf LME's EL‐MIST model indicated that the functional response of the Gulf's fisheries resources underwent significant reorganizations during the study period, primarily driven by basin‐scale climate variability and shifting fishing fleets’ targets, effort, and associated regulatory environments, over time. Using EL‐MIST, we identified four unique organizational regimes, and we were able to describe the prominent differences in the underlying resources’ structure and function between those dynamic regimes. We also detail three pertinent ecological regime shifts over the 30‐yr study period and present evidence for the dominating effects of commercial and recreational fishing activities, along with the Atlantic Multidecadal Oscillation and its teleconnected processes, on the organization of fisheries resources. Support for the hypothesis that fishing intensity can affect the relative resilience of a fishery ecosystem that is undergoing climatic and physical–chemical environmental changes is also presented here, as are results implicating a slowing trend in the rates of change across many relevant ecosystem‐level fisheries‐management indicators. When implementing EBFM, the EL‐MIST protocol is useful for distilling the large amounts of information gathered by large‐scale monitoring efforts and assessments. This new framework is transferable across management systems, is ideal for use with current indices and metrics, has the flexibility to address a wide range of inquiries, and can help disentangle complex fisheries ecosystem dynamics to help better inform management recommendations.