This paper is concerned with experimental analyses on the vibration behaviors of a horizontal pipe containing gas–liquid two-phase flow with different flow patterns. The effects of flow patterns and superficial velocities on pressure fluctuations and structural responses are evaluated in detail. Numerical simulations on the fluid–structure interactions within the pipe are carried out using the volume of fluid method and the finite element method. A strongly partitioned coupling method is adopted to ensure the compatibility and equilibrium interface conditions between the fluid and the elastic pipe. The accuracy of the numerical solutions is confirmed by comparing with experimental results. It is found that the fluctuation frequency of the pressure fluctuations of the two-phase flow ranges from 0 Hz to 5 Hz. The standard deviation (STD) value of the pressure fluctuation of the two-phase flow increases with an increase in the superficial liquid velocity, and the maximum magnitude appears in slug flows. The vibration responses of the pipe exhibit strong dependence on the momentum flux of the two-phase flow, which mainly excites the fundamental flexural vibration mode of the pipe. The magnitude of vertical vibration response of the pipe is equal to that of the lateral vibration response, and the vibration response measured at the middle of the pipe does not contain the second-order operating mode. Moreover, the STD value of the structural responses of the pipe increases proportionally with an increase in the gas flowrate, while the predominant vibration frequency of the pipe slightly increases.