Plankton data from 1997 to 2005 were used to examine impacts of a managed drawdown, subsequent drought and resulting historic low water levels (during 2000 and 2001) on the zooplankton of Lake Okeechobee, Florida. Prior to the drought the lake supported less than 150 ha of submerged vegetation. Following the drought, over 15,000 ha of submerged vegetation developed around the lake shore and conditions favored greater survival of age 0 fish. The zooplankton changed significantly from the pre-to post-drought period, including: (a) a near-complete loss of all dominant species of cladocerans and rotifers; and (b) an abrupt transition to a community with over 80% of total biomass comprised of Arctodiaptomus dorsalis, a calanoid copepod previously described as being resistant to fish predation. These changes persisted over a 5 year post-drought sampling period. In contrast, there were no systematic changes in biomass of bacteria, phytoplankton, inedible cyanobacteria, algal cell size, suspended solids, or any other physical or chemical attributes known to affect zooplankton in shallow lakes. Evidence points towards increased predation by fish, and perhaps invertebrates, as factors responsible for loss of cladocerans and rotifers following the drought, and indicates a need for future research to link changes in water level to shifts in predation pressure in this and other shallow lakes.