As humanity develops strategies to manage and adapt to climate change, potential changes to carbon cycles are of increasing interest. The potential sensitivity of carbon sources and sinks in lakes may be of global importance, yet the direction and magnitude of possible changes are poorly understood across entire lake-rich regions. We used a spatially explicit simulation model of water and carbon cycling to explore the potential behavior of 6739 lakes and watersheds to changes in climate. Our study site was the Northern Highland Lake District of northern Wisconsin and the Upper Peninsula of Michigan. We developed two perturbation scenarios built from observed extreme high and low precipitation and evaporation values. Despite a spatially uniform change in precipitation across the region, individual lakes responded differently. Hydrologic responses were mostly predictable at both individual and regional scales, but the routing of carbon in lakes was both more sensitive and varied. We estimate that in today's climate, 7.3E+10 g of carbon are vented annually from lake surfaces in the District to the atmosphere. Compared to today's climate, total regional flux of carbon from lake surfaces was 31% higher in the wet scenario and 45% lower in the dry scenario. Some measures of carbon fluxes (such as net ecosystem production) appear to change uniformly and gradually at the regional scale, though aggregate change was driven primarily by considerable changes in relatively few large lakes. The simulations demonstrate that simple, spatially homogeneous perturbations in these complex connected watersheds can have both predictable and surprising effects.