The study of flow-acoustic coupling mechanism is crucial to the development of large diameter ultrasonic flowmeters applied in industrial piping systems. An ultrasonic flowmeter with an inner diameter of 500 mm is simulated, mainly focusing on the coupling mechanism between the flow field and acoustic field. The distribution characteristics of flow field in the ultrasonic flowmeter are analyzed. The effects on the flow field and acoustic field caused by the installing structure of transducers are revealed. The acoustic characteristic and the acoustic pressure distribution on the transducer receiver end face are shown. The flow velocity and the system deviation of the ultrasonic flowmeter are calculated by the difference in travel times between the downstream and the upstream propagations. The in-depth study of complex flow-acoustic coupling mechanism has significant meanings for the improvement of measurement performance of the ultrasonic flowmeter.