An isolation trench is a simple and effective method to isolate structural vibrations originating from sources of vibration other than earthquakes (machines, traffic, explosions, etc.); however, there is still not a conclusive depth of the isolation trench for frame structures. To investigate the isolation effect of a trench in the frame structure designed for ground vibration, both a field test and finite element analysis were conducted to analyze the reduced effect of the vibration. The vibration reduction analysis was based on the dynamic equation and wave theory. Considering the vibration control of an industrial plant frame, a soil-trench-building finite element model was built to analyze the vibration characteristics of the floor before and after the open isolation trench structure was used. According to the model, a dynamic test was carried out on the frame structure to assess the effect of the vibration reduction by introducing the trench. The results showed that the depth of the trench was the dominating factor in vibration isolation. When the depth of the trench reached 1~1.3 times the wavelength of the Rayleigh wave, the damping effect was the strongest. the width of the trench has little effect on the vibration isolation efficiency, and the trench must be maintained at a certain distance from the building to ensure the vibration damping efficiency. The vibration of each floor was obviously reduced after the trench was built. The vibration damping effect of the trench was significant.