Dissolved oxygen concentrations are declining in the bottom waters of many lakes around the world, posing critical water quality concerns. Throughout my dissertation, I assessed how bottom-water dissolved oxygen may mediate the effects of climate and land use change on water quality in lakes. First, I characterized causes of variation in summer bottom-water temperature and dissolved oxygen. I demonstrated that spring air temperatures may play a greater role than summer air temperatures in shaping summer bottom-water dynamics. I then characterized the effects of declining bottom-water oxygen concentrations across diverse scales of analysis (i.e., using microcosm incubations, whole-ecosystem oxygenation experiments, and data analysis of >600 widespread lakes). I found that low dissolved oxygen concentrations contributed to release of nutrients and organic carbon from lake sediments, potentially altering the role of lakes in global biogeochemical cycles. Importantly, I also found support for a previously-hypothesized Anoxia Begets Anoxia feedback, whereby bottom-water anoxia (i.e., no dissolved oxygen) in a given year promotes increasingly severe occurrences of anoxia in following summers. This finding demonstrates the need for forecasts of future oxygen dynamics in lakes, as management actions to preempt the first occurrence of anoxia will be more effective than actions to restore ecological function after oxygen concentrations have already declined. To build the capacity for such forecasts, I led a systematic review of ecological forecasting literature that characterized the state of the field, emerging best practices, and relative predictability of four ecological variables. Combined, my dissertation provides a mechanistic examination of the effects of climate change on water quality in lakes worldwide, ultimately helping to anticipate, mitigate, and preempt future water quality declines. / Doctor of Philosophy / Changes in climate and land use have caused dissolved oxygen concentrations to decline in many lakes around the world. These declines are concerning because low oxygen concentrations can cause substantial water quality problems. If we could better predict future water quality, we may be able to develop more effective lake management programs. To help meet this need, I analyzed how dissolved oxygen has mediated historical changes in water quality, and how dissolved oxygen may affect water quality in the future. I focused on bottom-water (rather than surface-water) dissolved oxygen, because bottom waters are more likely to experience very low oxygen concentrations that can lead to water quality problems. I started by assessing the drivers of summer bottom-water dissolved oxygen in 615 lakes. Across these lakes, spring air temperatures played a greater role than summer air temperatures in shaping summer bottom-water temperature and dissolved oxygen. I then characterized the effects of declining bottom-water oxygen concentrations using small-scale incubations in the lab, manipulations of oxygen concentrations in a whole reservoir, and data analysis across 656 lakes. I found that low dissolved oxygen conditions led to the release of nutrients and organic carbon from lake sediments, which may worsen water quality. Importantly, I also found support for a feedback effect, whereby low bottom-water dissolved oxygen in one summer perpetuates oxygen declines in following summers. This finding motivates the need for forecasts of future dissolved oxygen concentrations, as management actions to stop the first occurrence of low oxygen concentrations will be more effective than actions to restore water quality after oxygen concentrations have already started to decline. To build capacity for lake oxygen forecasts, I synthesized many published papers that have predicted future ecological states, and I documented proposed best practices in this emerging field. Ultimately, by advancing our understanding of how climate and land use change affect water quality in lakes worldwide, my dissertation research will help to anticipate, mitigate, and preempt future water quality declines.