<h2>Summary</h2> High-entropy alloys (HEAs) hold great promise for efficient catalyst discovery in a virtually unlimited compositional space. The controllable incorporation of multiple metal elements into low-dimensional nanomaterials with tailored structure merits untold scientific and applicable potential; however, it remains a great challenge using previous high-temperature synthetic techniques. Hence, we report a general reduction-diffusion method for constructing a library of atomic-thick Pt-based HEA nanowires (NWs) with up to ten components. We have identified that the initial formation of Pt NWs and the nucleation rate of other transition metals are the key points in forming a uniform HEA single-phase solid solution. Our method can be used to synthesize 26 kinds of multimetallic NWs, including 17 HEAs. The high-entropy design can introduce severe lattice distortion in NWs, thereby altering the strain distribution and electronic structure, which enables the HEA NWs with specific components to exhibit outstanding catalytic performance in hydrogen oxidation reaction and hydrogen evolution reaction.