The aims of this study were to estimate the machinability and machining accuracy of polymer-based CAM blocks using the merlon fracture test model specified in ISO 18675: 2022. Three hybrid disc blanks (MazicDuro, HC Disk, and Enamic) and three polymethyl methacrylate (PMMA) disc blanks (PMMA Disk, PMMA Block, and MazicTemp Hybrid) were tested in this study. The machinability was evaluated by assigning scores according to the fracture range of merlons with areas divided by ten vertical planes. The machining accuracy was evaluated by superimposing methods via CAD reference data and CAD specimen data. Within the limits of this study, a thickness of 0.3 mm is recommended for the clinical application of polymer-based CAD/CAM blocks in dental restorations that require superior machinability and accuracy. In addition, the machinability and machining accuracy tests of polymer-based CAM blocks are expected to provide guidelines for preparing accurate dental restorations.