Hypereutrophic Grand Lake St Marys (GLSM) is a large (52 km2), shallow (mean depth ~ 1.5 m) reservoir in an agricultural watershed of western Ohio (USA). GLSM suffers from extensive cyanobacterial harmful algal blooms (cHABs) that persist much of the year, resulting in total microcystin concentrations that are often above safe contact levels. Over two summers (2020 and 2021), two phosphorus (P) binding agents (alum and lanthanum/bentonite clay Phoslock, respectively), in conjunction with a P-binding algaecide (SeClear) in 2021, were applied to a 3.24-ha enclosure to mitigate cHAB activity and create a ‘safe’ recreational space for the public. We evaluated these applications by comparing total phosphorus (TP), total microcystin, total chlorophyll, and phycocyanin concentrations within the enclosure and the adjacent lake. Some evidence for short-term reductions in TP, microcystin, chlorophyll, and phycocyanin concentrations were observed following each P binding treatment, but all parameters rapidly returned to or exceeded pre-application levels within 2–3 weeks after treatment. These results suggest that in-lake chemical treatments to mitigate cHABs are unlikely to provide long-lasting benefits in these semi-enclosed areas of large, shallow, hypereutrophic systems, and resources may be better applied toward reducing external nutrient loads (P and nitrogen) from the watershed.