Fault diagnosis plays an important role in complex and safety-critical systems such as nuclear power plants (NPPs). With the development of artificial intelligence (AI), extensive research has been carried out for fast and efficient fault diagnosis based on intelligent methods. This paper presents a review of various AI-based system-level fault diagnosis methods for NPPs. We first discuss the development history of AI. Based on this exposition, AI-based fault diagnosis techniques are classified into knowledge-driven and data-driven approaches. For knowledge-driven methods, we discuss both the early if–then-based fault diagnosis techniques and the current new theory-based ones. The principles, application, and comparative analysis of the representative methods are systematically described. For data-driven strategies, we discuss single-algorithm-based techniques such as ANN, SVM, PCA, DT, and clustering, as well as hybrid techniques that combine algorithms together. The advantages and disadvantages of both knowledge-driven and data-driven methods are compared, illustrating the tendency to combine the two approaches. Finally, we provide some possible future research directions and suggestions.