Anaerobic digestion of sewage sludge is limited at the hydrolysis stage of the process. The goal of this study was to assess the effects of sludge retention times and ultrasound pretreatment on the ammonium concentration and organic matter transformation in anaerobic digesters treating sewage sludge. To achieve this, two laboratory-scale semicontinuous anaerobic digesters were operated for a period of over 70 d, including a control reactor and another fed by pretreated sludge. Both anaerobic systems were fed with mixed sludge (50%/50% primary/secondary treatment) in mesophilic conditions (37 °C), with solid retention times (SRT) of 7.5 d (Phase I) and 3 d (Phase II). The performance of the anaerobic digestion process was assessed in terms of the methane yield and the total and soluble chemical organic demand, total solids, and volatile solids removal. The results showed that the ultrasound pretreatment caused an increase of around 22.2% in CODt removal for an SRT of 7.5 d. Meanwhile, an SRT of 3 d resulted in a decrease of up to 92.4% in CODt removal. The performance in terms of biogas production and organic matter removal was significantly affected by the SRT reduction to 3 d, showing that the process is not viable in these conditions.