Multiple advanced reactor designs envision deployment scenarios that feature reactor operations with significantly reduced operating staff compared to present reactors, or even feature fully autonomous operations. Since many of these new reactor designs, like small modular reactors (SMRs) and microreactors, also include extended fuel cycles which limit inspection intervals, load-following capabilities, and reduced access to critical components, safe and reliable semi- or fully autonomous operations must be enabled through an on-line monitoring (OLM) system that effectively detects and diagnoses any faults in the reactor. This paper presents the development of the Fault Detection Module of the previously proposed intelligent OLM system: the Fault Detection and Diagnosis Monitoring System (FDDMS). The Fault Detection Module monitors various plant parameters from 86 sensors throughout the nuclear power plant and accurately defines operations as nominal or abnormal. The methodology leverages the advantages of unsupervised learning and semi-supervised optimization data-driven techniques to successfully detect any fault in the system in real-time without fault information a priori. This allows the Fault Detection Module to identify any unknown fault that may affect the system. When integrated with the rest of the FDDMS architecture, the Fault Detection Module provides power transient dependent fault detection by using a separate model for steady state, ramping up in power, and ramping down in power operations. This makes the FDDMS especially applicable for load-following reactor systems. The Fault Detection Module architecture features a dimensionality reduction algorithm followed by an anomaly detection method. Three dimensionality reduction techniques: 1) Principal Component Analysis (PCA), 2) Deep Neural Network Autoencoder (DNNAE), and 3) Convolutional Neural Network Autoencoder (CNNAE); and three anomaly detection methods: 1) One-Class Support Vector Machine (OC-SVM), 2) Clustering (DBSCAN), and 3) Reconstruction Error (RecErr) thresholding were compared to find the best model for each power transient dataset. Precision rates, recall rates, F1-scores, and accuracies were used to compare model performance. The best models produced total accuracies of 94.50%, 93.63%, and 91.76% for the steady state, ramp up, and ramp down datasets, respectively, or 99.19%, 98.97%, and 97.09% when omitting 1%-severe fault cases. Specifically, the best performing models for the steady state, ramp up, and ramp down cases were the CNNAE-RecErr, DNNAE-DBSCAN, and CNNAE-RecErr, respectively. Recall rates were calculated for various fault types at multiple severity levels. The results show that the Fault Detection Module can identify any type of fault in the system with a delay of a few seconds on average. Additionally, robustness against noisy sensor data was tested, with models maintaining 100% accuracy at various levels of noise, and an illustrative real-time application of the methodology is provided.