Sulfide minerals have similar flotation behavior using the commonly-used collectors such as xanthate due to its low selectivity to active metal ions on sulfide minerals, which leads to difficulties separating chalcopyrite from galena and pyrite. In this work, dibutyl phosphonate (HDBP) was investigated as a collector for chalcopyrite. Flotation tests confirmed that HDBP can selectively and effectively collect chalcopyrite at low concentrations and at environment-friendly pH. This was supported by the results of X-ray photoelectron spectrometry (XPS), electrochemical tests and Density Functional Theory (DFT) simulations. It can be inferred from the XPS results that single-bonded and double-bonded oxygen atoms in the HDBP structure undergo chemisorption with Cu atoms on the surface of chalcopyrite, while HDBP barely interacts with galena and pyrite. This was supported by the results of DFT simulations which showed that the stable adsorption of HDBP on the surface of chalcopyrite is formed by the four-member chelation ring with the P–O–Cu and P=O–Cu bonds with a higher adsorption energy of −133.01 kcal/mol. Electrochemical tests suggested that the corrosion potential and current of the chalcopyrite electrode increase significantly after using HDBP due to the formation of the new oxides. However, for galena and pyrite, there were no obvious changes, which further indicated that HDBP has a strong and selective reactivity to chalcopyrite. The strong affinity of HDBP for Cu atoms means that it has strong potential as a collector for the selective separation of copper-bearing minerals.