Controllable one-to-one coalescence of surfactant-stabilized nanoliter water drops is successfully achieved from wetting-induced drop engulfing in microfluidics by surrounding one of the drops with a thin layer of immiscible wetting fluid. This wetting layer can spread over the other drop to drain away the liquid film between the two drops, thereby inducing coalescence. This innovative approach is totally spontaneous and highly potential in a myriad of fields, such as quantitative analysis, microreaction, and high-throughput injection. To demonstrate this potential, we successfully perform the drop-coalescence-triggered microreaction in microchannels for pH indicator and syntheses of functional materials including micro- and nanoparticles.