Kintampo South District in the Bono East Region of Ghana is dominated by metavolcanic and metasedimentary rocks of the Birimian and the Voltaian Supergroups, which are reported to show aquifer complexities and quality issues. Therefore, assessment of groundwater evolution and quality is important in this area because of the growing need for groundwater for both agricultural and residential use. The people heavily rely on agriculture as their main source of livelihood, and the agricultural practices could potentially impact the groundwater quality. Consequently, this research aimed to evaluate groundwater appropriateness in the Voltaian aquifers of the Kintampo South District for irrigation and consumption. Irrigation water quality indices, geochemical modeling, hydrochemical graphing, and chemometric analysis were all used in the assessment. The investigation reported potassium ion (K+) as the principal cation in the groundwater, showing concentrations within the range of 0.200 to 61.0 mg/L and a mean of 6.32 mg/L. Bicarbonate (HCO3−) is also the major anion in the samples with values that vary from 2.00 to 238 mg/L and a mean of 27.8 mg/L. Geospatial mapping indicates that these predominant ions show higher concentrations in the central part of the study area. Groundwater evolved from K-SO4-HCO3 to Na-HCO3-Cl water types and other mixed forms, which are influenced by atmospheric precipitation and rock weathering. Geochemical modeling reveals that undersaturation of the groundwater occurs in relation to all the silicate and carbonate minerals in the aquifer. However, most samples show positive correlation with these minerals, suggesting precipitation under pre-existing conditions. Chemometric analysis indicated that the chemical composition of groundwater is controlled by human-induced and geogenic activities. With respect to all hydrochemical parameters, the groundwater is largely deemed safe for residential use based on the computed Water Quality Index values. The groundwater in the district is also appropriate for irrigation, according to irrigation indices of water quality such as the Wilcox diagram, sodium adsorption ratio (SAR), Electrical conductivity (EC), magnesium ratio (MR), and sodium percent (Na%).