Although mechanical ventilation is a life-saving therapy for patients with severe lung disorders, the microbubble flows generated during ventilation generate hydrodynamic stresses, including pressure and shear stress gradients, which damage the pulmonary epithelium. In this study, we used computational fluid dynamics to investigate how gravity, inertia, and surface tension influence both microbubble flow patterns in bifurcating airways and the magnitude/distribution of hydrodynamic stresses on the airway wall. Direct interface tracking and finite element techniques were used to simulate bubble propagation in a two-dimensional (2D) liquid-filled bifurcating airway. Computational solutions of the full incompressible Navier–Stokes equation were used to investigate how inertia, gravity, and surface tension forces as characterized by the Reynolds (Re), Bond (Bo), and Capillary (Ca) numbers influence pressure and shear stress gradients at the airway wall. Gravity had a significant impact on flow patterns and hydrodynamic stress magnitudes where Bo > 1 led to dramatic changes in bubble shape and increased pressure and shear stress gradients in the upper daughter airway. Interestingly, increased pressure gradients near the bifurcation point (i.e., carina) were only elevated during asymmetric bubble splitting. Although changes in pressure gradient magnitudes were generally more sensitive to Ca, under large Re conditions, both Re and Ca significantly altered the pressure gradient magnitude. We conclude that inertia, gravity, and surface tension can all have a significant impact on microbubble flow patterns and hydrodynamic stresses in bifurcating airways.