Methane hydrates in fine‐grained continental slope sediments often occupy isolated depth intervals surrounded by hydrate‐free sediments. As they are not connected to deep gas sources, these hydrate deposits have been interpreted as sourced by in situ microbial methane. We investigate here the hypothesis that these isolated hydrate accumulations form preferentially in sediments deposited during Pleistocene glacial lowstands that contain relatively large amounts of labile particulate organic carbon, leading to enhanced microbial methanogenesis. To test this hypothesis, we apply an advection‐diffusion‐reaction model with a time‐dependent organic carbon deposition controlled by glacioeustatic sea level variations. In the model, hydrate forms in sediments with greater organic carbon content deposited during the penultimate glacial cycle (~120–240 ka). The model predictions match hydrate‐bearing intervals detected in three sites drilled on the northern Gulf of Mexico continental slope, supporting the hypothesis of hydrate formation driven by enhanced organic carbon burial during glacial lowstands.