Minho River, also called Miño (in Spain), extends to about 300 km from Spain to Portugal. The source of the river lies in Spain and in the last 75 km, the river defines the border between Portugal and Spain. Under the scope of a cooperation project between North Portugal and Galicia region of Spain, titled: "Valorization of the natural resources of the Minho/Miño drainage basin", seven water-sampling campaigns were carried out during the last 2 years in Minho River basin. Seven sampling sites were selected along the international stretch, and five were chosen in the main Portuguese and Spanish tributaries of Minho River. Water quality based on the physicochemical and microbial parameters was assessed. According to the Portuguese legislation for surface waters, the international section of Minho River presents a reasonably good water quality (BOD5 <5 mg/L, TNK <2 mg/L, and total phosphorous <1 mg P/L). Valença and Louro were found to be the most polluted sampling sites and Louro the most polluted tributary (maximum values observed: TSS = 26 mg/L, BOD5 = 6.6 mg O2/L, COD = 20.8 mg O2/L, total nitrogen = 9.9 mg N/L; minimum value observed: OD = 1.3 mg O2/L). A one-dimensional stream water quality model QUAL2Kw was calibrated using data measured in field surveys along the international stretch of Minho River. QUAL2Kw was also used to predict the impact of flow conditions, discharges, and tributaries on the water quality of international stretch of Minho River, essential to establish proposals for management and planning of Minho River Basin.