The paper considers the neural network application to detect microstructure defects in dissimilar welded joints using the acoustic emission (AE) method. The peculiarity of the proposed approach is that defect detection is carried out taking into account a priori information about the properties of the AE source and the acoustic waveguide parameters of the testing structure. Industrial process pipelines with dissimilar welded joints were studied as the testing object, and diffusion interlayers formed in fusion zones of welded joints were considered microstructure defects. The simulation of AE signals was carried out using a hybrid method: the signal waveform was determined based on a finite element model, while the amplitudes of AE hits were determined based on a physical experiment on mechanical testing of dissimilar welded joints. Measurement data from industrial process pipelines were used as noise realizations. As a result, a data sample was formed that considered the parameters of the AE source and the parameters of the acoustic waveguide with realistic noise parameters and a signal-to-noise ratio. The proposed method allows for a more accurate determination of the waveform, spectrum, and amplitude parameters of the AE signal. Greater certainty in the useful signal parameters allows for achieving a more accurate and reliable classification result. When using a backpropagation neural network, a percentage of correct classification of more than 90% was obtained for a data set in which the signal-to-noise ratio was less than (−5 dB) in 90% of cases.