© 2020 Elsevier Ltd An effective management tool for the spatial prioritization of the Cozumel Reefs National Park (CRNP), using a systematic approach, is an urgent need for the conservation of one of the most important Marine Protected Areas (MPAs) in Mexico. In this study, we integrated a model using seascape metrics, the spatio-temporal variation of substrate coverage, and frequency of reef use for SCUBA diving, to systematically identify priority areas for conservation within the CRNP. We identified seven habitat types: sand beds, reef, two habitats of macroalgae beds (high and low cover), and seagrass beds with three different densities, using a supervised classification on a SPOT 7 (2017) satellite image (overall accuracy of 84%, Kappa of 0.79). Matlab and Fragstats were used to calculate seascape metrics (habitat β-diversity, shape complexity and connectivity). A change detection analysis, comparing the SPOT 7 with an Ikonos image, was utilized to estimate seascape change between 2004 and 2017. Interviews with diving operators were also obtained, to calculate the frequency of visits to different reefs within the CRNP. A weighted overlay analysis, integrating the metrics mentioned above, was used to identify priority areas for conservation. We identified five areas, where management strategies need to be strengthened (e.g. limiting the number of visitors). The current subzonation of the protected area does not reflect the conservation priorities identified by our analysis. However, given that the CRNP management plan is in the process of being updated, the obtained results can help the CRNP managers improve the conservation efforts based on a systematic and robust approach, ensuring the design and implementation of cost-effective strategies for the conservation of the MPA.