• Wastewater was collected from different-scale WWTPs. • Raw wastewater without pre-treatment was assessed. • Outdoor cultures were conducted under natural condition in different seasons. • Strategy for enhanced outdoor biomass yield and stability was developed. Coupling microalgae cultivation with wastewater treatment is a promising strategy to purify the waste streams and harvest the enhanced biomass production. In this study, an oleaginous alga Scenedesmus obliquus that was isolated from the dairy wastewater was examined for its bioremediation of municipal wastewater. Water samples, including raw and treated ones, were collected from three wastewater treatment plants at different scales. Under indoor conditions, S. obliquus showed strong nutrient removal efficiency, with nitrogen and phosphorus removal rates being over 99%. The alga grew faster in the raw wastewater (specific growth rates: 0.37−0.45 d−1), whereas more lipids accumulated in the treated wastewater (31.45–35.74%of dry weight). The raw wastewater-based culture was subsequently enlarged by using panel photo-bioreactors (PBRs) in semi-continuous mode. Such outdoor cultivations were conducted twice in different seasons, reflecting the impacts of environmental fluctuation. Results showed that under the natural condition, the hydraulic retention time (HRT)-based culture was significantly impacted by the changeable temperatures and illumination; instead, replacing the medium (i.e. raw wastewater) following biomass concentration rather than HRT made the culture system more stable. An average biomass productivity of 0.22 g L−1 d−1 was obtained, regardless of the changing environmental conditions. These findings may advance the knowledge of employing S. obliquus for raw wastewater treatment at the industrial scale. [ABSTRACT FROM AUTHOR]