Abstract The 2D/1D mixed‐dimensional van der Waals heterostructures have great potential for electronics and optoelectronics with high performance and multifunctionality. The epitaxy of 1D micro/nanowires on 2D layered materials may efficiently realize the large‐scale preparation of 2D/1D heterostructures, which is critically important for their practical applications. So far, however, only the wires of Bi 2 S 3 , Te, and Sb 2 Se 3 have been epitaxially grown on MoS 2 or WS 2 . Here, it is reported that the epitaxial growth of 1D CsPbBr 3 nanowires on 2D Bi 2 O 2 Se nanoplates through a facile vertical vapor deposition method. The CsPbBr 3 wires are well aligned on the Bi 2 O 2 Se plates in fourfold symmetry with the epitaxial relationships of [001] CsPbBr3 ||[200] Bi2O2Se and [1‐10] CsPbBr3 ||[020] Bi2O2Se . The photoluminescence results reveal that the emission from CsPbBr 3 is significantly quenched in the heterostructure, which implies the charge carriers transfer from CsPbBr 3 to Bi 2 O 2 Se. The waveguide characterization shows that the epitaxial CsPbBr 3 wires may efficiently confine and guide their emission, which favors the light absorption of Bi 2 O 2 Se. Importantly, the photocurrent mapping and spectra of the devices based on these 2D/1D heterostructures prove that the epitaxial CsPbBr 3 wires remarkably enhances the photoresponse of Bi 2 O 2 Se, which indicates these heterostructures can be applied in high‐performance optoelectronic devices or on‐chip integrated photonic circuits.