Pipeline transportation systems play an increasingly essential role in the development of the economy. An accurate location of leakage is important to reduce economic losses and maintain the safe operation of pipelines. In this article, a pipeline leakage detection method based on infrasound and negative pressure waves (NPWs) is adopted. This method can locate the leakage only by collecting the infrasound and pressure signals at the first station of the pipeline, which effectively solves the disadvantages of low positioning accuracy of a signal and easily produces false alarms. In this article, the signal denoising method of cross-spectral analysis combined with ensemble empirical mode decomposition (EEMD) was adopted. First, the leakage signals of sound waves and NPWs are processed by EEMD to obtain a series of intrinsic mode functions (IMFs). The characteristic frequency band is obtained by cross-spectral analysis of the leakage signal. Within this frequency band, the dominant component of the leakage source signal is divided by correlation analysis, and the IMF component is reconstructed to complete the signal denoising. When compared to the single signal pipeline leak detection method, the positioning accuracy of this article showed a 1–3 m improvement on average.