The synthesis of mixed-dimensional van der Waals heterostructures with controlled alignment by chemical vapor deposition (CVD) technique remains a big challenge due to the complex epitaxial growth mechanism. Herein, we report the epitaxial growth of mixed-dimensional Bi2S3/WS2 heterostructures by a two-step CVD method. Bi2S3 crystals grown on 2D WS2 monolayers exhibit 1D feature with the preferred orientation, indicating a strong epitaxial growth behavior at the 1D/2D interface. Furthermore, the heterostructure was carefully characterized by transmission electron microscopy, which reveals the preferential growth of Bi2S3 nanowires along the zigzag edge of WS2 monolayers. The experimental results are also consistent with the theoretical calculations by DFT, where the preferred orientation possesses minimal surface energy. The strong interaction between Bi2S3 and WS2 enables efficient charge transfer of photogenerated carriers at the heterointerface, which leads to a largely improved light harvesting capability with the highest responsivity of ∼48.1 AW-1 and detectivity of ∼5.9 × 1012 Jones.