Inherent differences between naturally-formed lakes and human-made reservoirs may play an important role in shaping zooplankton community structure. For example, because many reservoirs are created by impounding and managing lotic systems for specific human purposes, zooplankton communities may be affected by factors that are unique to reservoirs, such as shorter water residence times and a reservoir's management regime, compared to natural lakes. However, the environmental factors that structure zooplankton communities in natural lakes vs. reservoirs may vary at the continental scale and remain largely unknown. We analyzed data from the 2007 U.S. Environmental Protection Agency's National Lakes Assessment and the U.S. Army Corps of Engineers' National Inventory of Dams to compare large-bodied crustacean zooplankton communities (defined here as individuals retained by 0.243 mm mesh size) in natural lakes and reservoirs across the continental U.S. using multiple linear regressions and regression tree analyses. We found that large-bodied crustacean zooplankton density was overall higher in natural lakes compared to reservoirs when the effect of latitude was controlled. The difference between waterbody types was driven by calanoid copepods, which were also more likely to be dominant in the >0.243 mm zooplankton community in natural lakes than in reservoirs. Regression tree analyses revealed that water residence time was not a major driver of calanoid copepod density in natural lakes but was one of the most important drivers of calanoid copepod density in reservoirs, which had on average 0.5-year shorter water residence times than natural lakes. Reservoirs managed for purposes that resulted in shorter residence times (e.g., hydroelectric power) had lower zooplankton densities than reservoirs managed for purposes that resulted in longer residence times (e.g., irrigation). Consequently, our results indicate that water residence time may be an important characteristic driving differing large-bodied zooplankton dynamics between reservoirs and natural lakes.