The pressure leaching mechanism of chalcopyrite was studied by both leaching tests and in-situ electrochemical measurements. The effects of leaching temperature, oxygen partial pressure, and calcium lignosulphonate, on copper extraction and iron extraction of chalcopyrite pressure leaching were investigated. The leaching rate is accelerated by increasing the leaching temperature from 120 to 150 °C and increasing oxygen partial pressure to 0.7 MPa. The release of iron is faster than that of copper due to the formation of iron-depleted sulfides. Under the optimal leaching conditions without calcium lignosulphonate, the copper and iron extraction rates are 79% and 81%, respectively. The leaching process is mixedly controlled by surface reaction and product layer diffusion with an activation energy of 36.61 kJ/mol. Calcium lignosulphonate can effectively remove the sulfur passive layer, and the activation energy is 45.59 kJ/mol, suggesting that the leaching process with calcium lignosulphonate is controlled by surface chemical reactions. Elemental sulfur is the main leaching product, which is mixed with iron-depleted sulfides and leads to the passivation of chalcopyrite. Electrochemical studies suggest that increasing the oxygen partial pressure leads to increasing the cathodic reaction rate and weakening the passivation of chalcopyrite.