Non-precious metal-based efficient electrocatalysts with superior activity and stability for the hydrogen evolution reaction (HER) are useful in solving energy and environmental crises. Herein, monodisperse inverse opal-like MoxC (α-MoC1-x/β-Mo2C) nanospheres were synthesized via a facile strategy to adjust the intrinsic activity and maximize the exposed active sites. In particular, the MoxC-0.4 with the optimal composition of α-MoC1-x/β-Mo2C (0.56/0.44) demonstrated a superior HER performance in 0.5 M H2SO4 with a small Tafel slope of 48 mV dec−1 and remarkable stability. Such prominent performance not only benefits from the inverse opal-like structure that provides more active sites for HER, but also should be ascribed to the strong synergistic effect between α-MoC1-x and β-Mo2C. Based on theoretical calculations, it is further verified that the synergistic effect of MoxC-0.4 is originated from the optimization of interaction with the H* induced by the heterostructure. Furthermore, this work will broaden our vision for highly efficient hydrogen production by bridging the microscopic structure with macroscopic catalytic performance.