This study suggests a hybrid method of signed digraph and partial least squares for the fault diagnosis of chemical processes. Using the local qualitative relationships of each variable in a signed digraph, a process is decomposed into subprocesses to allow for the reliable diagnosis of multiple faults. A partial least-squares model is built for the estimation of each measured variable in each decomposed subprocess. To handle the process dynamics accurately, the input of the partial least-squares model uses both the current values and the past values of the process variables. In each case, the measured and estimated values are compared to diagnose the fault. A case study of a continuously stirred tank reactor illustrates the conclusion that the proposed method greatly improves the accuracy, resolution, and reliability of the diagnosis.