In this work, a simple one-step hydrothermal approach was used to successfully manufacture a novel indium doped molybdenum trioxide (In-MoO3) photocatalyst for enhancing the photocatalytic degradation of Rhodamine B (RhB) under simulated light. The structural characterization of In-MoO3 confirms successful addition of indium ions to the MoO3 lattice. Importantly, the performance of the doped samples was significantly enhanced when the doping mass of indium accounted for 5% under simulated light, and the RhB degradation rate reached 96.2%. Even after four cycles, the doped sample proved to maintain excellent cycling stability. The proposed photocatalytic mechanism for the RhB degradation by In-MoO3 is presented. It is revealed that ·OH acts as the primary active species in this photocatalytic system, while ·O2− also plays a supporting role. Indium doping improves the light absorption and effectively reduces the interfacial charge transfer resistance and bandgap width, leading to significant progress in the photocatalytic performance of MoO3.