Lithium disilicate (LDS) glass ceramics are among the most common biomaterials in conservative dentistry and prosthodontics, and their wear behavior is of paramount clinical interest. An innovative in vitro model is presented, which employs CAD/CAM technology to simulate the periodontal ligament and alveolar bone. The model aims to evaluate the effect of the abutment rigidity on the wear resistance of the LDS glass ceramic. Two experimental groups (LDS restorations supported by dental implants, named LDS-on-Implant, or by hybrid ceramic tooth replicas with artificial periodontal ligament, named LDS-on-Tooth-Replica) and a control group (LDS-Cylinders) were compared. Fifteen samples (n = 15) were fabricated for each group and subjected to testing, with LDS antagonistic cusps opposing them over 120,000 cycles using a dual axis chewing simulator. Wear resistance was analyzed by measuring the vertical wear depth (mm) and the volume loss (mm3) on each LDS sample, as well as the linear antagonist wear (mm) on LDS cusps. Mean values were calculated for LDS-Cylinders (0.186 mm, 0.322 mm3, 0.220 mm, respectively), LDS-on-Implant (0.128 mm, 0.166 mm3, 0.199 mm, respectively), and LDS-on-Tooth-Replica (0.098 mm, 0.107 mm3, 0.172 mm, respectively) and compared using one-way-ANOVA and Tukey’s tests. The level of significance was set at 0.05 in all tests. Wear facets were inspected under a scanning electron microscope. Data analysis revealed that abutment rigidity was able to significantly affect the wear pattern of LDS, which seems to be more intense on rigid implant-abutment supports compared to resilient teeth replicas with artificial periodontal ligament.