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 Bi2S3, Te, and Sb2Se3 have been epitaxially grown on MoS2 or WS2. Here, it is reported that the epitaxial growth of 1D CsPbBr3 nanowires on 2D Bi2O2Se nanoplates through a facile vertical vapor deposition method. The CsPbBr3 wires are well aligned on the Bi2O2Se 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 CsPbBr3 is significantly quenched in the heterostructure, which implies the charge carriers transfer from CsPbBr3 to Bi2O2Se. The waveguide characterization shows that the epitaxial CsPbBr3 wires may efficiently confine and guide their emission, which favors the light absorption of Bi2O2Se. Importantly, the photocurrent mapping and spectra of the devices based on these 2D/1D heterostructures prove that the epitaxial CsPbBr3 wires remarkably enhances the photoresponse of Bi2O2Se, which indicates these heterostructures can be applied in high‐performance optoelectronic devices or on‐chip integrated photonic circuits.