Consuming fish exposed to cyanobacterial harmful algal blooms (HABs) may be a major route of microcystin toxin exposure to humans. However, it remains unknown whether fish can accumulate and retain microcystins temporally in waterbodies with recurring seasonal HABs, particularly before and after a HAB event when fishing is active. We conducted a field study on Largemouth Bass, Northern Pike, Smallmouth Bass, Rock Bass, Walleye, White Bass, and Yellow Perch to assess the human health risks to microcystin toxicity via fish consumption. We collected 124 fish in 2016 and 2018 from Lake St. Clair, a large freshwater ecosystem in the North American Great Lakes that is actively fished pre- and post-HAB periods. Muscles were analyzed using the 2-methyl-3-methoxy-4-phenylbutyric acid (MMPB) Lemieux Oxidation method for total microcystins, which was used to perform a human health risk assessment for comparison against fish consumption advisory benchmarks available for Lake St. Clair. From this collection 35 fish livers were additionally extracted to confirm the presence of microcystins. Microcystins were detected in all livers at widely varying concentrations (1–1500 ng g−1 ww), suggesting HABs are an underappreciated and pervasive stressor to fish populations. Conversely, microcystin levels were consistently low in muscles (0–15 ng g−1 ww) and presented negligible risk, empirically supporting that fillets may be safely consumed before and after HAB events following fish consumption advisories.