Despite a growing awareness of the importance of inland waters in regional and global carbon (C) cycles, particularly as sources of the greenhouse gases carbon dioxide (CO2) and methane (CH4), very little is known about C sources and fluxes in the Laurentian Great Lakes, Earth's largest surface freshwater system. Here, we present a study of CH4 dynamics in Lake Erie, which has large spring algae blooms linked to fertilizer runoff and followed by hypoxia, as well as an extensive network of natural gas wells and pipelines in Canadian waters. Lake Erie is a positive source of CH4 to the atmosphere in late summer, even in shallow regions without water column hypoxia. Stable isotopic measurements indicate that both biogenic and thermogenic CH4 contribute to emissions from Lake Erie. We estimate that Lake Erie emits 1.3 ± 0.6 × 105 kg CH4‐C d−1 in late summer, with approximately 30% of CH4 derived from natural gas infrastructure. Additional work is needed to determine the spatial and temporal dynamics of CH4 emissions from Lake Erie and to confirm estimates of source contribution. Studies of the C cycle in large lakes are not as straightforward as those in smaller lakes, as, in addition to O2 availability, subsurface currents and high winds may exert significant control over dissolved CH4 patterns. If climate warming and increasing precipitation intensity lead to increased algal biomass and/or greater extent and duration of hypoxia, this may increase emissions of CH4 from Lake Erie in a positive feedback to climate change.