Chemical quality and extent of pollution in effluent-contaminated irrigation water collected from two sectors (X and Y) of peri-urban southern regions of Khyber Pakhtunkhwa, Pakistan, were investigated. Various physico-chemical parameters like pH, EC, TS, TSS, TDS, TH, cations (Na, K, Li, Ca, Mg), anions (Cl, F, HCO, NO, SO), and heavy metals (Cr, Fe, Cu, Zn, Pb, Cd) were determined. The data indicated wide ranges of variation in all the parameters. Concentration of physico-chemical properties such as EC, TS, TSS, TH, Li, Ca, Mg, and HCO and heavy metals (Cr, Fe, Cu, and Cd) exceeded WHO permissible limits. The distribution of heavy metals in two sampling areas followed the increasing order as Fe > Cr > Cd > Cu > Pb > Zn. The Piper diagram showed that water in the region was of alkaline type. Strong positive correlations were observed among most of the parameters; however, pH was negatively correlated with most of the parameters. According to principle component analysis, parameters causing variations in water quality were mainly EC, TDS, TS, TSS, TH, Na, K, Ca, Mg, F, NO, SO, Cr, Fe, Cu, and Zn. Linear regression analysis revealed that heavy metals like Cr, Fe, and Cu concentrations were strongly correlated having an R value of 0.92 at P ≤ 0.001 with pH. Overall, the results suggested that irrigation water of the area was not fit for irrigation purposes and might cause serious threats for safe, healthy food and feed production. Proper monitoring of water of the said area should be carried out, and quality of irrigation water should be checked from time to time.