The co-contamination of aquatic systems with antimony (Sb) and humic acid (HA) is a global concern due to their potential risks to human health and environment. In this research, three-level-three-variable Box–Behnken design (BBD) was investigated for simultaneous Sb(III) and total organic carbon (TOC) removal responses from groundwater by use of ferric chloride (FC) as a coagulant. This study focuses on three operating variables, including initial Sb(III) concentration (100, 550, and 1000 μg/L), HA concentration (2, 6, and 10 mgC/L) and FC dosages (20, 60, and 100 mg/L). The proposed quadratic model presented good correlation with experimental values having R2 and adjusted R2 values of response variables (Sb(III): 0.9981 and 0.9956) and (TOC: 0.9935 and 0.9851), respectively. The most pronounced influence of FC dosage was observed in the removal responses of TOC and Sb(III). Interestingly, the model revealed that a high level of FC dosage had the same TOC removal potential regardless of increasing HA concentration. The statistical model for both Sb(III) and TOC responses was used to optimize the experimental conditions. Moreover, the experimental results were successfully validated with predicted values having high accuracy. The sludge volume produced for studied variables followed the decreasing order as FC dosage > HA concentration > Sb(III) concentration. Under optimum conditions, 0.45 mL/L sludge volume was produced in the treatment of ground water in Nawabshah. In general, the results of the current study may provide some insights into the predictability of simultaneous removal performance of Sb species and organic substances from groundwater.