Charge separation/transfer is generally believed to be the most key factor affecting the efficiency of photocatalysis, which however will be counteracted if not taking the active site engineering into account for a specific photoredox reaction. Here, a 3D heterostructure composite is designed consisting of MoS2 nanoplatelets decorated on reduced graphene oxide‐wrapped TiO2 nanotube arrays (TNTAs@RGO/MoS2). Such a cascade configuration renders a directional migration of charge carriers and controlled immobilization of active sites, thereby showing much higher photoactivity for water splitting to H2 than binary TNTAs@RGO and TNTAs/MoS2. The photoactivity comparison and mechanistic analysis reveal the double‐edged sword role of RGO on boosted charge separation/transfer versus active site control in this composite system. The as‐observed inconsistency between boosted charge transfer and lowered photoactivity over TNTAs@RGO is attributed to the decrease of active sites for H2 evolution, which is significantly different from the previous reports in literature. The findings of the intrinsic relationship of balanced benefits from charge separation/transfer and active site control could promote the rational optimization of photocatalyst design by cooperatively manipulating charge flow and active site control, thereby improving the efficiency of photocatalysis for target photoredox processes. A 3D cascade heterostructure consisting of MoS2 nanoplatelets uniformly decorated on the RGO‐wrapped TiO2 nanotube arrays is designed via a step‐by‐step integration strategy. The double‐edged sword role of graphene on boosted charge separation/transfer versus active site control is revealed.