(1) Background: Aesthetic dentistry has become one of the most dynamic fields in modern dental medicine. Ceramic veneers represent the most appropriate prosthetic restorations for smile enhancement, due to their minimal invasiveness and highly natural appearance. For long-term clinical success, accurate design of both tooth preparation and ceramic veneers is of paramount importance. The aims of this in vitro study were to assess the stress in anterior teeth restored with Computer-Aided Design (CAD) and Computer-Aided Manufacturing (CAM) ceramic veneers and compare the resistance to detachment and the fracture of ceramic veneers prepared using two different designs. (2) Methods: Sixteen lithium disilicate ceramic veneers were designed and milled using the CAD-CAM technology and divided into two groups according to the preparations (n= 8): Group 1, conventional (CO), with linear marginal contour and Group 2, crenelated (CR), the latter with our novel (patented) sinusoidal marginal design. All samples were bonded to anterior natural teeth. The mechanical resistance to detachment and fracture was investigated by applying bending forces on the incisal margin of the veneers in order to determine which type of preparation leads to better adhesion. An analytic method was employed, as well, and the results of the two approaches were compared. (3) Results: The mean values of the maximum force recorded at the veneer detachment were 78.82 ± 16.55 N for the CO group and 90.20 ± 29.81 N for the CR group. The relative increase, equal to 14.43%, demonstrated that the novel CR tooth preparation provided higher adhesive joints. In order to determine the stress distribution within the adhesive layer, a finite element analysis (FEA) was performed. The statisticalt-test showed that the mean value of the maximum normal stresses is higher for the CR-type preparations. (4) Conclusions: The patented CR veneers represent a practical solution to augment the adhesion and mechanical properties of ceramic veneers. The obtained results demonstrated that CR adhesive joints triggered higher mechanical and adhesive forces, which subsequently led to a higher resistance to detachment and fracture.