The performance of a novel low-maintenance tube reactor for ultrasonic treatment of sludge has been evaluated. The effects of sonication on the release of soluble chemical oxygen demand (sCOD) and anaerobic digestibility of raw and digested sewage sludge as well as agricultural sludge were studied. Results suggest that solubilization and digestibility is dependent on both type of sludge and the energy input. Digested and raw sludge showed high degree of solubilization, however, methane production was only increased for digested sludge. Agricultural sludge was not significantly affected by ultrasonic treatment neither concerning sCOD release nor methane production. The configuration of the ultrasonic system (serial vs. parallel operation) did not show a significant difference in both sCOD release and methane production. However, parallel operation tends to perform better for digested sludge, while serial operation tends to perform better for raw sludge. The strongest effect was observed for the treatment of digested sludge by increasing the methane production by more than 60%, although with a very intensive energy input of more than 5,000 kJ per kg total solids. Hence, tube reactors seem to be an attractive alternative to sonotrode-based systems achieving similar performance at low maintenance with great potential especially for digested sludge.