Chemical weathering of bedrock plays an essential role in the formation and evolution of Earth’s critical zone. Over geologic time, the negative feedback between temperature and chemical weathering rates contributes to the regulation of Earth climate. The challenge of understanding weathering rates and the resulting evolution of critical zone structures lies in complicated interactions and feedbacks among environmental variables, local ecohydrologic processes, and soil thickness, the relative importance of which remains unresolved. We investigate these interactions using a reactive-transport kinetics model, focusing on a low-relief, wetland-dominated karst landscape (Big Cypress National Preserve, South Florida, USA) as a case study. Across a broad range of en- vironmental variables, model simulations highlight primary controls of climate and soil biological respiration, where soil thickness both supplies and limits transport of biologically derived acidity. Consequently, the weathering rate maximum occurs at intermediate soil thickness. The value of the maximum weathering rate and the precise soil thickness at which it occurs depend on several environmental variables, including precipitation regime, soil inundation, vegetation characteristics, and rate of groundwater drainage. Simulations for en- vironmental conditions specific to Big Cypress suggest that wetland depressions in this landscape began to form around beginning of the Holocene with gradual dissolution of limestone bedrock and attendant soil develop- ment, highlighting large influence of age-varying soil thickness on weathering rates and consequent landscape development. While climatic variables are often considered most important for chemical weathering, our results indicate that soil thickness and biotic activity are equally important. Weathering rates reflect complex inter- actions among soil thickness, climate, and local hydrologic and biotic processes, which jointly shape the supply and delivery of chemical reactants, and the resulting trajectories of critical zone and karst landscape develop- ment.