A promising system consisting of Up-flow Anaerobic Sludge Blanket (UASB) and Down-Flow Hanging Sponge (DHS) system was investigated for removal of COD, BOD5 fractions, ammonia and faecal coliform from domestic wastewater. The combined system was operated at different HRTs of 16, 11 and 8 h. The results indicate that increasing the total HRT from 8 to 16 h significantly (p < 0.05) improves the CODtotal and BOD5total removal mainly as a result of a higher removal of CODsoluble, BODsoluble, CODparticulate and BODparticulate. The main part of coarse suspended solids was removed in the UASB reactor (76.4 ± 18%) and the remaining portion was adsorbed and/or enmeshed and degraded in the biomass of the DHS system. The combined system achieved a substantial reduction of total suspended solids (TSS) resulting in an average overall percentage removal of 94 ± 6% (HRT = 16 h) and 89.5 ± 7.8% (HRT = 8 h). Faecal coliform reduction was significantly improved when increasing the total HRT from 8 to 16 h. Residual counts of faecal coliform were 3.1 × 103/100 ml at a total HRT of 16 h, and 2.8 × 104/100 ml at total HRT of 8 h, corresponding to overall removal efficiency of 99.97 ± 0.03 and 99.6 ± 0.3% respectively. Despite the increase of ammonia concentration as a result of protein hydrolysis in the UASB reactor, a substantial removal of ammonia was achieved in the DHS system. The results obtained show that decreasing the OLR imposed to DHS system from 2.6 to 1.6 kg COD/m3·d significantly (p < 0.05) improves the removal efficiency of ammonia by a value of 29%. However, the removal efficiency of ammonia is not further increased when decreasing the OLR from 1.6 to 1.3 kg COD/m3·d. The discharged sludge from UASB + DHS system exerts a good settling property and partially stabilized. DHS profile results have shown that the major part of COD, BOD5, and TSS was removed in the upper part of the system, consequently, the nitrification process was occurring in the lower part of the DHS system.