Granitic groundwaters are important resources in arid regions. However, they are not always pure due to having appreciable amounts of trace elements. The present study was conducted to investigate chemical compositions for finding controls on distribution of heavy metals and natural radioelements (U and Th) in groundwater resources of Shir-Kuh granitoid aquifer (SGA), central Iran. Thirty water samples were collected and analyzed for major and trace elements. The average values of electrical conductivity (EC) and pH are 624 μs/cm and 7.5, respectively. The dominant groundwater type is Ca-HCO3, as a result of the calcite dissolution and biotite weathering. Principal component analysis in support of mass balance studies recognizes dissolution of fracture-filling sediments and rock mineral weathering as the main factors enhancing major ions in SGA. These processes also release trace elements in decreasing order of Sr > Ba > Sn > W > Cu > U > Zn > Th. Weathering of biotite enclosing accessory minerals of monazite and zircon is introduced as the main source of radio-trace elements in SGA. Health concerns are currently related to U in drinking groundwater, as the maximum concentration (13.6 μg/L) approaches the Iranian drinking standard of 15 μg/L, in response to the oxidizing nature of the groundwater, calcite dissolution-related mobilization, and the degree of the water–rock interactions.