Abstract The survivability and reliability of commercial electronic components under very high thermo-mechanical loads are improved using underfilling and potting methods. Potting protects from operating conditions such as moisture, water, or corrosive agents. Furthermore, potting offers damping against shock and vibrations, heat dissipation, and structural support. Being one of the most cost-efficient methods, potting greatly increases reliability and therefore reduces costs for replacements and repairs. It also addresses trapped hot air issues better than other restraint technologies. In potted electronic assemblies, interfacial delamination at the epoxy and printed circuit board (PCB) interface has been one of the major failure modes. Interfacial delamination happens at the epoxy/PCB interface under dynamic shock loads, which leads to failures at the solder interconnects of the electronic components. Sustained operation and storage at elevated temperatures change the interfacial characteristics at the epoxy/PCB interface. This research is focused on interfacial failure mechanics at epoxy/PCB interfaces with high-temperature isothermal aging. In the selection of the epoxy potting material and the reliability assessments of the supplemental restraint systems, fracture parameters such as steady-state strain energy release rate stress and fracture toughness are critical. Rectangular beam specimens of the epoxy/PCB interface are fabricated for different potting compounds, and the fracture behavior is studied under quasi-static monotonic three-point and four-point bend loads. One of the main differences between three-point and four-point bend loading is that the maximum bending stress occurs at the midpoint under the point of loading of the specimen in three-point bending, whereas the peak stress is distributed over the section of the specimen between the loading points in four-point bending. Four different potting compounds with diverse properties have been studied. The recommended curing schedule from the manufacturer has been chosen and followed for all the potting compounds. The epoxy/PCB interfacial samples are aged at a high temperature of 100 °C for 30–180 days. Damage has been assumed to happen at the epoxy/PCB interface under dynamic loads. The critical load of crack initiation for the epoxy/PCB interface has been determined from the experimental findings, and it is used in the computation of fracture toughness values. The fracture toughness values are compared for the various epoxy/PCB systems based on the number of days of thermal aging and the method of flexure testing. A cohesive zone model has been constructed for predominantly mode-I delamination with four-point bend stress to predict the interfacial delamination behavior at the epoxy/PCB interfaces. It has been assumed that the bulk material is linear elastic during the bending load. The cohesive zone has been modeled at the interface, where the interfacial fracture has been assumed to occur. The fracture behavior in the simulation is predicted based on the fracture parameters determined through the experiment. The computed cohesive zone parameters are unique to the interfaces, and they can be used across various applications with the same epoxy/PCB interface to predict interfacial delamination and to select a more suitable potting material.