In order to study the effect of water-loaded pressure on the ultrasonic guided wave signals, the dispersion curve and wave structure of guided wave in the pipe are analyzed by using the semi-analytical finite element (SAFE) method. The L(0,2) mode guided wave is selected in the detection experiment. A waterproof clamp that can withstand a pressure of 30 MPa is designed to encapsulate the piezoelectric transducer on the pipe. The encapsulated pipe is placed into a pressure chamber for the pressure cycle test, where the pressure varies between 0 MPa and 30 MPa. The guided wave signals of the heathy pipe and the damaged pipe with 5% area loss are collected during the pressure cycle experiments in order to analyze the effect of the water-loaded pressure on the guided wave signals. The experimental results show that the waterproof clamp has good waterproof and pressure-resistant properties, and at the same time, the water-loaded pressure does not have a significant effect on the amplitude of the L(0,2) modal waveguide signal.