Developing an efficient method for chloramphenicol (CAP) detection is of great significance for food safety. Arginine (Arg) was selected as a functional monomer. Benefiting from its excellent electrochemical performance, which is different from traditional functional monomers, it can be combined with CAP to form a highly selective molecularly imprinted polymer (MIP) material. It overcomes the shortcoming of poor MIP sensitivity faced by traditional functional monomers, and achieves high sensitivity detection without compounding other nanomaterials, greatly reducing the preparation difficulty and cost investment of the sensor. The possible binding sites between CAP and Arg molecules were calculated by molecular electrostatic potential (MEP). A low-cost, non-modified MIP electrochemical sensor was developed for the high-performance detection of CAP. The prepared sensor has a wide linear range from 1 × 10−12mol L−1to 5 × 10−4mol L−1, achieves a very low concentration CAP detection, and the detection limit is 1.36 × 10−13mol L−1. It also exhibits excellent selectivity, anti-interference, repeatability, and reproducibility. The detection of CAP in actual honey samples was achieved, which has important practical value in food safety.