Ultrasound-assisted enzymatic hydrolysis is a recent process, increasingly employed for plant biomass liquefaction and the recovery of soluble biomolecules. However, to our knowledge, it has never been used on seaweeds, particularly wet ones. The aim of this study was to compare the efficiency of three processes on the liquefaction of the red seaweed Grateloupia turuturu Yamada: enzyme-assisted extraction (EAE), ultrasound-assisted extraction (UAE), and their combination, ultrasound-assisted enzymatic hydrolysis (UAEH). These comparisons will allow the identification as to which process achieves the highest extraction yield of water-soluble compounds. For this purpose, experiments were conducted at 40 °C for 6 h using an enzymatic cocktail of four industrial carbohydrases and an original ultrasonic flow-through reactor. After 6 h, similar profiles were observed between EAE and UAE with the recovery of 71–74 % of the initial material into the soluble phase. However, when these processes were combined, up to 91 % solubilized material was observed in the same time, with a synergistic effect after 2 h. From a biochemical point of view, UAEH improved the extraction of nitrogen and carbon compounds and, more precisely, carbohydrates and amino acids. This study demonstrates that ultrasound improved the enzymatic hydrolysis, probably by an increase in the mass transfer and a disruption of the thallus due to the implosion of the cavitation bubbles generated. UAEH is clearly an efficient procedure for the liquefaction of wet seaweeds, enabling the recovery of valuable components.