Purpose: To compare the fracture resistance of five different groups of chairside CAD/CAM molar crowns fabricated from various lithium disilicate ceramic materials (LDC): one conventional precrystallized CAD/CAM LDC, two novel precrystallized LDCs, and one fully crystallized LDC tested both with and without optional sintering. Materials and Methods: A total of 60 chairside CAD/CAM lithium disilicate molar crowns (n = 12 per group) with 1.5-mm occlusal thickness and a 1.0-mm chamfer finish were designed and fabricated with a chairside CAD/CAM system (CEREC, Dentsply Sirona). The restorations were divided into five groups: (1) IPS e.max CAD; (2) Amber Mill; (3) Straumann n!ce; (4) Straumann n!ce with optional sintering; and (5) Supreme CAD. Restorations were cemented using conventional resin luting cement and primer system to 3D-printed resin dies. Bonded restorations were loaded for 100,000 cycles with 275-N force, and the load at break (LB) and peak load (PL) until fracture were measured. SEM images of fracture surfaces on the printed dies were obtained. Results: Fracture resistance was significantly different depending on the material. Supreme CAD showed the highest fracture resistance (LB: 1,557.2 N; PL: 1,785.8 N), followed by Amber Mill (LB: 1,393.0 N; PL: 1,604.2 N) and IPS e.max CAD (LB: 1,315.7 N; PL: 1,461.9 N). Straumann n!ce without (LB: 862.4 N; PL: 942.9 N) and with the optional sintering (LB: 490.4 N; PL: 541.0 N) showed significantly lower fracture resistance than the others. Conclusion: The fracture resistance of chairside CAD/CAM lithium disilicate molar crowns varied depending on the material, and the novel materials did not perform as well as the conventional equivalents. Fully crystallized lithium disilicate ceramic block materials showed lower fracture resistance than precrystallized counterparts and should be used with caution in the clinic, especially with optional sintering.