Shock load from industrial wastewater is known to harm the microbial activities of the activated sludge in wastewater treatment plants (WWTPs) and disturb their performance. This study developed a system monitoring the activated sludge activities based on the relative oxygen uptake rate (ROUR) and explored the influential factors with wastewater and the activated sludge samples collected from a typical WWTP in the Taihu Lake of southern Jiangsu province, China. The ROUR was affected by the concentration of toxic substances, mixed liquid suspended solids (MLSS), hydraulic retention time (HRT) and pH. Higher toxin contents significantly decreased the ROUR and the EC50 value of Zn2+, Ni2+, Cr(VI), Cu2+, and Cd2+ was 13.40, 15.54, 97.56, 12.01, and 14.65 mg/L, respectively. The ROUR declined with the increasing HRT and MLSS above 2000 mg/L had buffering capacities for the impacts of toxic substances to some extent. The ROUR remained stable within a broad range pH (6–10), covering most of the operational pH in WWTPs and behaving as an appropriate indicator for monitoring the shock load. A toxicity model assessing and predicting the ROUR was developed and fitted well with experimental data. Coupling the ROUR monitoring system and toxicity model, an online early-warning system was assembled and successfully used for predicting the toxicity of different potential toxic metals. This study provides a new universal toxicity model and an online early-warning system for monitoring the shock load from industrial wastewater, which is useful for improving the performance of WWTPs.