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In Lake Erie, toxin-forming harmful algal blooms (HABs) occur following high concentrations of hydrogen peroxide (H 2 O 2 ). Correlation between H 2 O 2 concentrations and HABs revealed knowledge gaps on the controls of H 2 O 2 production in Lake Erie. One way H 2 O 2 is produced is upon absorption of sunlight by the chromophoric fraction of dissolved organic matter (CDOM). Rates of this photochemical production of H 2 O 2 may increase in proportion to the apparent quantum yield of H 2 O 2 ( Φ H 2 O 2 ,λ ) from CDOM. However, the Φ H 2 O 2 ,λ for H 2 O 2 production from CDOM remains too poorly constrained to predict the magnitude and range of photochemically produced H 2 O 2 , particularly in freshwaters like Lake Erie. To address this knowledge gap, the Φ H 2 O 2 ,λ was measured approximately biweekly from June–September 2019 in the western basin of Lake Erie along with supporting analyses ( e.g. , CDOM concentration and composition). The average Φ H 2 O 2 ,λ in Lake Erie was within previously reported ranges. However, the Φ H 2 O 2 ,λ varied 5-fold in space and time. The highest Φ H 2 O 2 ,λ was observed in the Maumee River, a tributary of Lake Erie. In nearshore waters of Lake Erie, the Φ H 2 O 2 ,λ decreased about five-fold from June through September. Integration of the controls of photochemical production of H 2 O 2 in Lake Erie show that the variability in rates of photochemical H 2 O 2 production was predominantly due to the Φ H 2 O 2 ,λ . In offshore waters, CDOM concentration also strongly influenced photochemical H 2 O 2 production. Together, the results confirm prior work suggesting that photochemical production of H 2 O 2 contributes but likely cannot account for all the H 2 O 2 associated with HABs in Lake Erie.