Groundwater is the major source of water supply for most uses in the rural settlements in Ghana. A groundwater flow model was calibrated for some aquifers of the southern Voltaian sedimentary system under steady-state conditions. The objective was to determine estimates of the hydraulic conductivities of the different hydrostratigraphic units of the southern Voltaian, and the distribution of recharge from precipitation. Data on the stable isotopes of oxygen and hydrogen from the study area suggest that groundwater recharge in the area is from rainfall. The calibrated steady-state model suggests that aquifer hydraulic conductivities in the study area range from 1.19 to 6.3 m/day. Hydrostratigraphic unit specific hydraulic conductivities are discussed. The calibrated recharge ranges from 3.81e−05 m/day to 6.0e−04 m/day, which represents 0.9–6% of the precipitation in the form of rainfall. Six distinct flowpaths have been defined using particle tracking. The particle tracking simulation suggests travel times in the range of 380 to 5,199 years from recharge areas to discharge areas along the flowpaths identified. A contaminant dropped at the recharge areas in the central sections of the model area would travel at these rates along the flowpaths, assuming that advection is the dominant transport process. Inverse geochemical modeling indicates the dissolution of albite, K-feldspars and anorthite, respectively, along flowpaths I and IV. The inverse modeling along flowpaths I and IV suggest the dissolution of albite, K-feldspar and anorthite, respectively, at 1.085e−06, 3.16e−08 and 3.168e−07 mmol/year.