As a new and promising family of two-dimensional (2D) materials, MBenes have attracted attention owing to their excellent stability, high electrical conductivity, and versatile physicochemical properties. However, studies on the intrinsic physical properties of MBenes, including superconductivity and band topology, are still relatively limited. In this study, we propose an effective strategy to regulate the superconducting and topological properties of Mo2B by combining surface functionalization and layer-number modulation based on first-principles calculations. Starting from pristine Mo2B in both 1T and 2H phases, we investigate hydrogenated (Mo2BH2), oxidized (Mo2BO2), and quintuple-layered (Mo2B3) derivatives. Thirteen thermodynamically and dynamically stable structures are identified. Among them, H1-Mo2BO2 and T2-Mo2B3 exhibit strong electron-phonon coupling and high superconducting transition temperatures of 32 K and 28 K, respectively. Notably, T2-Mo2B3 also shows non-trivial band topology characterized by the Z2 index of 1 and topological edge states. Our findings uncover rich properties in Mo2B-based MBenes and provide valuable insights for designing novel 2D materials with coexisting superconducting and topological states.