A well-defined WO3/Bi2S3 composite comprised of single-crystalline Bi2S3 nanowire (Bi2S3NW) layers on top of the WO3 nanoparticles (WO3NP) was synthesized via an in situ hydrothermal reaction. The single-crystalline Bi2S3 nanowires were uniformly grown on the surface of the WO3 nanoparticle layer. This in situ hydrothermal process is also a general route for the synthesis of well-aligned Bi2S3 nanowires on various metal oxide substrates, such as TiO2, BiVO4, and ZnO. Compared to the sole Bi2S3 electrode, the resulting WO3NP/Bi2S3NW composite showed enhanced photoelectrochemical activity. The origin of this enhanced activity is mainly attributed to the enhancement of charge separation on the Bi2S3 layer, due to the effective photogenerated electron transfer from the Bi2S3 conduction band to that of WO3. Furthermore, the single-crystalline longitudinal structure of the Bi2S3 nanowires can provide a direct electrical pathway through a single domain of nanowires.