In this paper, a CuCo–O@CNTs/NF electrode was successfully prepared and used for in-situ degradation of sulfamethoxazole (SMX) in an electro-Fenton-like system. Carbon nanotubes (CNTs) and coral-like copper-cobalt oxides were successively loaded on nickel foam (NF). CNTs contributed to improving the dispersibility and stability of copper-cobalt oxides, and the coral-like copper-cobalt oxide catalyst was anchored on CNTs without any adhesive. In the electro-Fenton-like system, dissolved oxygen can be reduced to superoxide anions in a one-electron step, which could be further transformed into hydrogen peroxide and then reacted with the active components on the electrode to generate reactive oxygen species (ROS) to participate in the degradation of SMX. Almost 100% SMX removal was obtained within 60 min in a wide near-neutral pH range (5.6–9.0), and the electrode could still achieve a 90.4% removal rate after ten recycle runs. Radical-quenching results showed that superoxide anions were the main species in the degradation of SMX. In addition, a possible degradation pathway of SMX was proposed. According to the result of toxicological simulations, the toxicity of the pollutant solution during the degradation process exhibited a decreasing trend. This study provides new insights for in-situ catalysis of electrodes with bimetallic active components to generate ROS for high-efficiency degradation of refractory organic pollutants.