Pipelines are one of the most efficient and economical methods of transporting fluids, such as oil, natural gas, and water. However, pipelines are often subject to leakage due to pipe corrosion, pipe aging, pipe weld defects, or damage by a third-party, resulting in huge economic losses and environmental degradation. Therefore, effective pipeline leak detection methods are important research issues to ensure pipeline integrity management and accident prevention. The conventional methods for pipeline leak detection generally need to extract the features of leak signal to establish a leak detection model. However, it is difficult to obtain actual leakage signal data samples in most applications. In addition, the operating modes of pipeline fluid transportation process often have frequent changes, such as regulating valves and pump operation. Aiming at these issues, this paper proposes a hybrid intelligent method that integrates kernel principal component analysis (KPCA) and cascade support vector data description (Cas-SVDD) for pipeline leak detection with multiple operating modes, using data samples that are leak-free during pipeline operation. Firstly, the local mean decomposition method is used to denoise and reconstruct the measured signal to obtain the feature variables. Then, the feature dimension is reduced and the nonlinear principal component is extracted by the KPCA algorithm. Secondly, the K-means clustering algorithm is used to identify multiple operating modes and then obtain multiple support vector data description models to obtain the decision boundaries of the corresponding hyperspheres. Finally, pipeline leak is detected based on the Cas-SVDD method. The experimental results show that the proposed method can effectively detect small leaks and improve leak detection accuracy.