In Lake Erie, toxin-forming harmful algal blooms (HABs) occur following high concentrations of hydrogen peroxide (H₂O₂). Correlation between H₂O₂ concentrations and HABs revealed knowledge gaps on the controls of H₂O₂ production in Lake Erie. One way H₂O₂ is produced is upon absorption of sunlight by the chromophoric fraction of dissolved organic matter (CDOM). Rates of this photochemical production of H₂O₂ may increase in proportion to the apparent quantum yield of H₂O₂ (Φ_H2O2,λ) from CDOM. However, the Φ_H2O2,λ for H₂O₂ production from CDOM remains too poorly constrained to predict the magnitude and range of photochemically produced H₂O₂, particularly in freshwaters like Lake Erie. To address this knowledge gap, the Φ_H2O2,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_H2O2,λ in Lake Erie was within previously reported ranges. However, the Φ_H2O2,λ varied 5-fold in space and time. The highest Φ_H2O2,λ was observed in the Maumee River, a tributary of Lake Erie. In nearshore waters of Lake Erie, the Φ_H2O2,λ decreased about five-fold from June through September. Integration of the controls of photochemical production of H₂O₂ in Lake Erie show that the variability in rates of photochemical H₂O₂ production was predominantly due to the Φ_H2O2,λ. In offshore waters, CDOM concentration also strongly influenced photochemical H₂O₂ production. Together, the results confirm prior work suggesting that photochemical production of H₂O₂ contributes but likely cannot account for all the H₂O₂ associated with HABs in Lake Erie.