Pine flatwoods (a mixture of cypress wetlands and managed pine uplands) is an important ecosystem in the southeastern U.S. However, long-term hydrologic impacts of forest management and climate change on this heterogeneous landscape are not well understood. Therefore, this study examined the sensitivity of cypress-pine flatwoods hydrology to climate change and forest management by using the physically based, distributed hydrologic modeling system, MIKE SHE. The model was first calibrated and validated with a long-term data set, and then applied using several hypothetical scenarios developed in north central Florida. Our study showed that MIKE SHE could simulate the temporal and spatial dynamics of the shallow ground-water table. The model also identified and confirmed three horizontal ground-water flow patterns at this study site. The modeling results suggested that forest removal and climate change (i.e., warming and drying) would have pronounced impacts on the ground-water table during the dry periods, but these impacts may be minor under wet conditions at this typical flatwoods landscape. At the landscape scale, depressional wetlands may have higher responses to tree removal and climate change than surrounding uplands.