Statement of problem: All glass-ceramic restorations can be constructed by milling with different CAD/CAM systems. Both 4-axis and 5-axis milling machines are widely used. However, controversy remains regarding which technique of construction provides better marginal accuracy and fracture resistance. Aim: Investigate the impact of two different milling protocols on the marginal accuracy and fracture resistance of advanced lithium disilicate glass-ceramic crowns. Materials and Methods: A typodont model was prepared following all-ceramic crown preparation principles. Crowns were fabricated using CEREC Tessera and then divided into two groups, each consisting of nine crowns: Group A (4-axis CEREC MCXL) and Group B (5-axis MCX5). The marginal accuracy was assessed at 30× magnification using a stereomicroscope. The fracture resistance was evaluated using a universal testing machine after crown cementation. Results: Group A (4-axis CEREC MCXL) exhibited significantly higher marginal accuracy (140.46 μm) compared to Group B (5 axis MCX5) (109.68 μm). Fracture resistance showed no significant differences between the groups. Conclusions: The number of CAD/CAM axes influences the marginal accuracy of advanced lithium disilicate glass-ceramic crowns, with the 4-axis milling machine demonstrating higher marginal accuracy compared to the 5-axis machine. However, there were no significant differences in fracture resistance between the two groups.