Settlement and metamorphosis of planktonic larvae into benthic adults is a critical part of a diverse range of marine invertebrate-mediated processes such as the formation of mussel beds and coral reefs, the recruitment of marine shellfisheries and the initiation of macrobiofouling. Although larval settlement and metamorphosis induced by natural chemical cues is widespread among marine invertebrates, their mechanisms of action remain poorly understood. Here, we identified that the molecular target of adenosine (an inducer of larval settlement and metamorphosis from conspecific adults in the invasive biofouling mussel Mytilopsis sallei) is adenosine kinase (ADK). Results of transcriptomic analyses, pharmacological assays, temporal and spatial gene expression analyses, and siRNA interference, suggest ATP-dependent phosphorylation of adenosine catalyzed by ADK, activates the downstream AMPK-FoxO signaling pathway, inducing larval settlement and metamorphosis in M. sallei. This study not only reveals the role of the ADK-AMPK-FoxO pathway in larval settlement and metamorphosis of marine invertebrates, but also deepens our understanding of the functions and evolution of adenosine signaling which is widespread in biology.