Antibiotic wastewater poses a great threat to the ecological environment and human health. Photocatalytic technology is an effective way to solve environmental pollution problems. In recent years, 2D/2D nanocomposites have received widespread attention because of their larger contact area, which can improve photocatalytic activity. However, the rapid synthesis of 2D/2D nanocomposites at low temperatures is still a challenge. Here, we demonstrated a facile one-step approach to synthesize 2D/2D ZnO nanosheet/rGO nanocomposites through microwave heating in a short time (20 min) for photodegradation of tetracycline (TC). Compared to the pure ZnO nanosheets, the ZnO/rGO-2 nanocomposites exhibited best photocatalytic activity under UV light. The enhanced photocatalytic performance could be attributed to introduction of GO nanosheets, which improves the specific surface area and pore structure and enhances the TC adsorption capacity. In addition, due to the interfacial coupling between ZnO and rGO, the charge was rapidly transferred and the recombination of photogenerated electron–hole pairs on the ZnO surface was inhibited. Our present work provided an efficient and low-temperature strategy for designing 2D/2D ZnO nanosheet/rGO photocatalysts and achieved gram-level production, which opens a new path to fabricate 2D/2D nanocomposites using microwave technology.