A new fabrication method of CdS nanobubbles with high photocatalytic activity has been explored under ambient conditions using SiO2 hard templates and microwave irradiation. The one-step Stober method has been used to produce SiO2 core nanospheres, onto which CdS shells have been readily and efficiently coated by 10 min microwave irradiation. The acid etching of the SiO2 cores has produced monodispersive CdS nanobubbles with outer diameters of 300, 370, and 400 nm with a uniform shell thickness of 11 nm. The CdS nanobubbles have been found to photocatalyze the degradation of rhodamine B efficiently under Xe-lamp irradiation via simultaneous reaction pathways of N-deethylation and conjugated-ring attack. It has been found that the degradation rate increases linearly with the concentration increase of the nanocatalyst but decreases nonlinearly with increasing nanobubble diameters. The pseudo-first-order degradation rate constant via the nanobubbles (0.081 min−1) was found to be about 20 times larger than that via the SiO2@CdS core@shell nanocomposites (0.0044 min−1) due to the nanoreactor confinement effect leading to a decrease in the activation energy of the reaction.