To investigate the effect of using different materials for the fabrication of implant abutments and crowns on the mechanical behavior of implant-supported single crowns after artificial aging. The materials were tested in different combinations to reveal whether using stiff or resilient materials as an abutment or a crown material might influence the fracture strength of the whole structure. A total of 40 implants (blueSKY, bredent GmbH & Co. KG) were restored with identical custom-made CAD/CAM abutments milled out of lithium disilicate or ceramic-reinforced PEEK and were divided into 5 test groups (n = 8 each). Forty crowns made of three different materials (zirconia, lithium disilicate, and ceramic-reinforced PEEK) were used to restore the abutments. Specimens were subjected to mechanical load up to 1,200,000 cycles in a chewing simulator (Kausimulator, Willytech) with additional thermal cycling. The surviving specimens were subjected to quasi-static loading using a universal testing machine (Z010, Zwick). PEEK abutments with zirconia crowns showed the highest median failure load (3890.5 N), while PEEK abutments with lithium disilicate crowns exhibited the lowest (1920 N). Fracture and deformation occurred in both crowns and abutments. The failure load of the restorations was influenced by the material of the abutment and the crown. Restoring PEEK abutments with zirconia crowns showed a high failure load and no screw loosening.