Many coastal states throughout the USA have observed negative effects in marine and estuarine environments caused by cyanotoxins produced in inland waterbodies that were transported downstream or produced in the estuaries. Estuaries and other downstream receiving waters now face the dual risk of impacts from harmful algal blooms (HABs) that occur in the coastal ocean as well as those originating in inland watersheds. Despite this risk, most HAB monitoring efforts do not account for hydrological connections in their monitoring strategies and designs. Monitoring efforts in California have revealed the persistent detection of cyanotoxins across the freshwater-to-marine continuum. These studies underscore the importance of inland waters as conduits for the transfer of cyanotoxins to the marine environment and highlight the importance of approaches that can monitor across hydrologically connected waterbodies. A HAB monitoring strategy is presented for the freshwater-to-marine continuum to inform HAB management and mitigation efforts and address the physical and hydrologic challenges encountered when monitoring in these systems. Three main recommendations are presented based on published studies, new datasets, and existing monitoring programs. First, HAB monitoring would benefit from coordinated and cohesive efforts across hydrologically interconnected waterbodies and across organizational and political boundaries and jurisdictions. Second, a combination of sampling modalities would provide the most effective monitoring for HAB toxin dynamics and transport across hydrologically connected waterbodies, from headwater sources to downstream receiving waterbodies. Third, routine monitoring is needed for toxin mixtures at the land–sea interface including algal toxins of marine origins as well as cyanotoxins that are sourced from inland freshwater or produced in estuaries. Case studies from California are presented to illustrate the implementation of these recommendations, but these recommendations can also be applied to inland states or regions where the downstream receiving waterbody is a freshwater lake, reservoir, or river.