In this study, three GR/Cu(II) (Green Rust/Cu(II)) composites (GR(SO4)/Cu(II), GR(CO3)/Cu(II), and GR(Cl)/Cu(II)) were synthesized and used to activate dioxygen under weakly acidic conditions. The change in the mechanism caused by three interlayer anions, CO32-, SO42-, and Cl-, was discussed for the first time. Both Cu(I) and H2O2 were generated during GR/Cu(II)-induced dioxygen activation, resulting in the rapid degradation of acetaminophen. The inconsistency between the reaction constant rates and oxidation reduction potential (ORP) order revealed the effects of the various types of interlayer ions. To further reveal the effects of the anions, the variations in the morphology and valence states of the composites were examined. To identify the rate-controlling step of dioxygen activation by the three composites, the production of reactive oxygen species (ROS) was investigated and compared. The combination of interlayer anions and metal ions changed the oxide morphology of the solid-phase materials. Furthermore, changes in the content of the reductive species (Fe(II) or Cu(I)) either enhanced or inhibited specific reaction steps. The results from this study could deepen our understanding of the effects of anions on dioxygen activation by transition metals and provide a basis for the study of oxidation reactions and mechanisms in the presence of various anions.