Awash River, one of the major rivers in Ethiopia which originate from the central highland area, crosses different extended agricultural farms as well as various industries which receives large effluents from different sources. Nineteen physicochemical parameters, as well as heavy metals (Fe, Zn, Cu, Pb, Cr, Cd and Ni), were quantified using atomic absorption spectroscopy in eight different sampling stations of Awash River. There was a significant spatial variation (p < 0.05) in average NO3-N, NH4-N, TN, BOD and COD values in Awash River. There is a strong and positive correlation between (pH and EC, r = 0.805), (WT and BOD, r = 0.774), (NO3-N and NO2-N, r = 0.901), (NO3-N and TN, r = 0.906), (NO3-N and TP, 0.830), (NH4-N and TN, r = 0.876), (NH4-N and COD, r = 0.848), (TN and TP, r = 0.819), (TN and COD, r = 0.941) during dry season and also between (WT and BOD, r = 0.704), (turbidity and NO3-N, r = 0.749), (turbidity and NO2-N, r = 0.722), (NO3-N and NO2-N, r = 0.921), (TP and COD, r = 0.789) during wet season. The results showed that the mean concentrations of metals ranked (high to low) Fe > Cr > Cu > Zn > Pb > Cd > Ni during dry season, whereas the concentration of heavy metals during wet season was in the following order of decreasing magnitude Fe > Cu > Zn > Pb > Cr > Cd > Ni. Buffer zones should be protected in order to control soil and agricultural nutrients from entering to Awash River. Moreover, industries at the upper stream area should be properly and adequately treat the wastewater before discharging to the Modjo as well as Awash River.