The flow field that forms at gas–liquid interfaces is strongly three-dimensional and extremely non-stationary, and it is considered difficult to understand. Among the types of gas–liquid two-phase flows, cross-flows, in which a fluid (gas phase) is blown into a main flow (liquid phase) having a velocity, are used to some mechanical applications via a chemical reaction. In recent years, several studies have been conducted on gas–liquid two-phase cross-flows using both experimental and numerical approaches. However, these studies have focused on the shape of bubbles. The mechanism of their breakup mechanism of the bubbles in the mainstream has not been understood. In this study, qualitative/quantitative experiments and numerical simulation are performed to clarify the bubble breakup mechanism. The three-dimensional dynamic behavior of the gas–liquid interface was captured by the numerical simulation using the commercial software ANSYS CFX and the particle image velocimetry (PIV).