A cough is a respiratory reflex for respiratory mucus clearance. The cough airflow dynamics can be characterized by three parameters, which are cough peak flow rate (CPFR), peak velocity time (PVT), and cough expired volume (CEV). In this study, the three-dimensional human respiratory airways from generation 0 to 5 are reconstructed from computerized tomography images. The non-Newtonian property of respiratory mucus is considered. The airflow–mucus interaction phenomenon has been analyzed in time and space based on the Eulerian wall film model. The maximum air velocity and wall shear stress could reach 38 m/s and 14 Pa, respectively, when the CPFR is 6 L/s. In addition, the influence of CPFR, PVT, and CEV on mucus clearance has been studied. The cough efficiency is used to quantify the mucus clearance. The results showed that increasing the cough peak flow rate has no noticeable effect on mucus clearance under normal and low mucus viscosity. Increasing the cough peak flow rate can effectively improve mucus clearance when the mucus viscosity becomes high. Specifically, the CEV has an apparent positive effect on clearing mucus regardless of the viscosity and thickness. This study provides a new research direction to improve mucus clearance by improving the CEV rather than the CPFR for patients with chronic obstructive pulmonary disease, neuromuscular disease, or other pulmonary diseases.