This study was carried out to assess the performance of the activated sludge process (ASP) for the treatment of oil refinery wastewater. Seasonal variation for temperature and the total dissolved solids (TDS) of wastewater were the key parameters examined. The treatment system is a batch-laboratory column that is continuously fed with oil refinery wastewater after physical separation of the surface oil layer in the refinery (API Separator). The determination of optimum operating conditions was performed for the treatment system at different temperatures ranging from 20 °C to 35 °C. Two main groups were examined: fresh wastewater (Group A) had an average TDS of less than 3 g/L, and saline wastewater (Group B) had an average TDS of 10–15 g/L. Results indicated that removal percentages in fresh wastewater (Group A) for chemical oxygen demand (COD), biological oxygen demand (BOD), oil and grease (O&G), phenols, and total suspended solids (TSS) were (76%–83%), (80.9%–92%), (83.5%–100%), and (94%–100%), respectively, while removal percentages in saline wastewater (Group B) for COD, BOD, O&G, phenols, and TSS were (76%–81%), (85.3%–95.8%), (87.5%–90%), (100%), and (93%–92%), respectively. The highest removal efficiency for pollution parameters was obtained at an average temperature of 25–35 °C. In conclusion, the overall treatment efficiency of fresh wastewater is better than that of saline wastewater. The quality of treated effluents achieved complies with the permissible limits of Egyptian regulations. Finally, ASP is efficient for the oxidation of organic matter applied to oil refinery wastewater with similar characteristics.