Abstract Due to the problems of the hydrolysis of wasted activated sludge (WAS), fermentation stage takes a long time and volatile fatty acids (VFAs) output efficiency is low. This study investigated the effect of ultrasound combined with Fenton (US/Fenton) pretreatment on the sludge disintegration and anaerobic fermentation. The sludge was treated by three different pretreatments respectively: ultrasound alone, Fenton alone and US/Fenton. Results show that after three pretreatments, sludge floc structure was disintegrated and oxidized, the sludge particle morphology after US/Fenton pretreatment was changed the most obviously. After US/Fenton, specific surface area was the largest and the particle size reduction was remarkable from 50.24 μm to22.44 μm. The SCOD concentration after US/Fenton was 3461.72 mg COD L-1, which was raised 1.73 times, 2.68 times and13.29 times as against that after ultrasound, Fenton and the untreated. The degree of disintegration (DDCOD) of the US/Fenton pretreatment was 15.4% which was greater than ultrasound pretreatment of 9.97% and Fenton pretreatment of 3.18%. The VFAs concentration after US/Fenton pretreatment reached a maximum value of 4594 mg COD L-1 at the eighth day, it was raised 31.8% and 70.15% as separately compared with the Fenton and ultrasound pretreatments. The pretreatments changed the VFAs composition and proportion. The highest HAC concentration after US/Fenton was 2039 mg COD L-1, which was 1.72 and 1.78 times of that in Fenton and ultrasound, respectively. This study showed that the US/Fenton pretreatment had a certain synergistic promotion effect on the sludge anaerobic fermentation. The ultrasound and Fenton co-work, the ability of the VFAs production is further improved.