Noble metal-free highly efficient cocatalysts are very important for cost efficient hydrogen fuel production. While most studies concentrate on single cocatalyst photocatalytic systems. Here, we report on the synthesis of Mn0.5Cd0.5S photocatalyst hetero-architecture with synergistic spatially separated dual cocatalysts Cu2-xS and MoS2 for highly efficient photocatalytic H-2 production. Through tactfully utilizing Cu2-xS/Mn0.5Cd0.5S nanoscale p-n junction to promote efficient transfer of photo-generated holes to Cu2-xS and MoS2 can be located exactly on the different positions where the photo-generated electrons must go through by photo-reduction of (NH4)(2)MoS4. Cu2-xS can be an oxidation active site to assemble photo-generated holes and MoS2 can capture and transport the photon-generated electrons. Therefore the photo-induced carriers can be efficiently separated and transferred to take part in photocatalytic reactions. The prepared Cu2-xS (0.015)/Mn0.5Cd0.5S/MoS2 (3 wt %) photocatalyst shows the highest H-2 production rate of 687.62 mu mol/h, which exceeds the rate of Mn0.5Cd0.5S and Mn0.5Cd0.5S loaded with Cu2-xS or MoS2 alone by 22, 1.7 and 3.48 times, respectively. This work provides a new thought to design efficient spatially separated and synergistic dual cocatalysts modified photocatalysts for H-2 production.