Ecosystem-based spatial management (EBSM) can provide a mechanism for a strategic and integrated plan-based approach to managing human activities in the marine environment. An EBSM approach was adopted in the Galapagos Marine Reserve (GMR) at the end of the 1990s with the adoption of marine zoning. The latter was created under a co-management regime to reduce conflicts among users arising over incompatible demands for ocean space, to mitigate the impact of human activities on sensitive ecological areas, and to contribute to the sustainability of Galapagos fisheries. Unfortunately, the promise of an EBSM approach in the GMR has not been matched by effectiveness in practice, in achieving the established management objectives. The aim of this paper is to evaluate the shortcomings and lessons learned related to planning, implementation, monitoring, evaluation and adaptation of the GMR’s marine zoning scheme, and to provide recommendations to better realize the potential value of the EBSM approach to co-managing the shellfisheries of the GMR.