This study evaluates the pollution of the Machángara River basin in Ecuador. For the assessment, water samples were pumped from the river for 1 to 4 h, with a representative water sample of 4 L collected. In the site and laboratory, the physicochemical parameters, carbamazepine (CBZ), and diclofenac (DIC) concentrations were measured using standardized analytical methods. On average, a temperature of 17.02 °C, pH of 7.06, electrical conductivity of 760.96 µS/cm, and turbidity of 83.43 NTU were found. Furthermore, the average solids content was 72.88, 495.47, and 568.35 mg/L for total suspended solids (TSS), total dissolved solids (TDS), and total solids (TS) in that order. The highest chloride concentration (Cl⁻ = 87.97 mg/L) was below the maximum permissible limit (MPL) based on the Ecuadorian regulations for surface and underground water for human consumption and domestic use, which only require conventional treatment. In contrast, levels of nitrate (NO₃⁻ = 27.75–288.25 mg/L) and nitrite in five points (NO₂⁻ = 2.02–5.42 mg/L) were higher than the MPLs. Moreover, sulfate (SO₄²⁻ = 34.75–110 mg/L) and phosphate (PO₄−P = 4.15–16.58 mg/L) contents caused turbidity and eutrophication in the river water., Additionally, concentrations of copper (Cu²⁺ = 0.002–0.071 mg/L), zinc (Zn²⁺ = 0.001–0.011 mg/L) and iron (Fe³⁺ = 0.000–0.287 mg/L) were within the permissible limits. On the other hand, carbamazepine concentrations in the Machángara River basin were below the limit of detection (LOD) up to a value of 0.121 mg/L. At the same time, diclofenac levels ranged from 9.32 to 48.05 mg/L. The concentration discrepancy for both pharmaceuticals is linked with the trend of drug consumption by Quito’s inhabitants. As measured in this investigation, meaningful amounts of CBZ and DIC are released to the Machángara River. Accordingly, the two pharmaceuticals in the river water may be dangerous for aquatic species.