The production of cassava flour generates wastewater with a high concentration of organic matter and nutrients, which gives this effluent potential as a source of both bioenergy and pollution. Thus, cassava wastewater needs to be properly treated prior to release into the environment. Different treatment processes are employed for this purpose, but studies involving up‐flow anaerobic sludge blanket (UASB) reactors without modifications are scarce due to the rapid acidification of cassava wastewater. Thus, the aim of the present study was to evaluate the rapid startup of UASB reactors at 30 °C for the cassava wastewater treatment. The reactor was operated under eight different conditions with a hydraulic retention time (HRT) of 8 or 12 h and organic loading rates (OLR) of 12.0 or 15.5 g COD · L−1 · d−1. The systems were evaluated based on chemical oxygen demand (COD) removal, the production of methane, and the stability of the volatile fatty acids/total alkalinity ratio. The UASB system with the best performance was that with the 8 h HRT and OLR of 12.0 g COD · L−1 · d−1, with COD removal rates ranging from 71 to 80 % and methane production of 0.260 L CH4 · g −1 CODremoved. The system offers a real‐scale prospect and is a promising option for the replacement of firewood in cassava flour toasting ovens, thereby contributing to the preservation of the semi‐arid Caatinga biome in northeastern Brazil.