Anthropogenic eutrophication has led to the increased occurrence of hypoxia in inland and coastal waters around the globe. While low dissolved oxygen conditions are known to be driven primarily by nutrient loading and water column stratification, the relative importance of these factors and their associated time scales are not well understood. Here, we explore these questions for Lake Erie, a large temperate lake that experiences widespread annual summertime hypoxia. We leverage a three-decade data set of summertime hypoxic extent (1985-2015) and examine the role of seasonal and long-term nutrient loading, as well as hydrometeorological conditions. We find that a linear combination of decadal total phosphorus loading from tributaries and springtime air temperatures explains a high proportion of the interannual variability in average summertime hypoxic extent (R2 = 0.71). This result suggests that the lake responds primarily to long-term variations in phosphorus inputs, rather than springtime or annual loading as previously assumed, which is consistent with internal phosphorus loading from lake sediments likely being an important contributing mechanism. This result also demonstrates that springtime temperatures have a substantial impact on summertime hypoxia, likely by impacting the timing of onset of thermal stratification. These findings imply that management strategies based on reducing tributary phosphorus loading would take several years to reap full benefits, and that projected future increases in temperatures are likely to exacerbate hypoxia in Lake Erie and other temperate lakes.