The drift-flux model (DFM) is of practical importance for analyzing gas–liquid flow in various applications, such as chemical reactors and nuclear power plants. This paper aims at developing an accurate flow-regime-independent DFM for estimating the void fractions of two-phase downward inclined flow. The effect of flow channel inclination on void fraction for downward two-phase flows was investigated comprehensively. First, 2868 data for void fractions of gas–liquid two-phase flows were summarized from 12 sources. The inclination angle ranged from 0° to 90°. Then, the existing drift-flux models were reviewed comprehensively. The existing models had poor predictive performance in terms of the whole experimental database. Therefore, a theoretically supported drift-flux model for downward inclined two-phase flow was established based on a deeper understanding of two-phase flow behavior. The influence of channel inclination angles on the distribution parameters and drift velocities was determined quantitatively. A total of 87.8% of estimated void fractions were within ±20% errors of experimental void fractions. The mean relative deviation, md, was −2.04%.