A novel hybrid architecture of 3D MnO2 nanosheet/N-doped graphene aerogel (S-MnO2/NGA) was controllably fabricated by a facile hydrothermal process and applied in peroxymonosulfate (PMS) activation for catalytic degradation. The catalytic efficiency of S-MnO2/NGA is notably higher than MnO2 nanotube/NGA (T-MnO2/NGA), NGA and MnO2 samples as well as some other conventional catalysts. The reaction rate constant (k) and activation energy for ibuprofen oxidation on S-MnO2/NGA are 0.149 min(-1) and 10.2 kJ/mol, respectively. The intimate interactions between 2D MnO2 nanosheet and 3D porous N-doped graphene aerogel are beneficial for synergistically enhancing the charge transfer and shortening the diffusion pathway of pollutants to promote mass transport, thus exerting an astonishing enhancement in the catalytic activities. Electron paramagnetic resonance (EPR) spectra and quenching tests verified that both hydroxyl (center dot OH) and sulfate radicals (SO4.-) were generated, while SO4 center dot- is the major reactive species responsible for ibuprofen oxidation. The positively linear correlation between the k values and pore volume of S-MnO2/NGA indicates that the 3D interconnected framework provides shorter pathways and more active sites for pollutant diffusion and oxidation. This approach contributes to a better understanding of the structure-activity relationship of 3D graphene-based aerogels in advanced oxidation processes (AOPs).