Background: The objective was to determine the optimal connector size and position within zirconia disks for implant-supported cantilever fixed dental prostheses (ICFDP). Methods: Two-unit ICFDPs (n = 60) were designed for the premolar region with connector sizes of either 9 or 12 mm2 and positioned in the enamel or dentin layer of two different types of zirconia disks. The restorations were milled and cemented onto zirconia implants. After simulated chewing for 1.2 Mio cycles, the fracture load was measured and fractures were analyzed. Results: No fractures of ICFDPs or along the implants were detected after simulated aging. The mean fracture load values were significantly higher for a connector size of 9 mm2 (951 N) compared with 12 mm2 (638 N). For the zirconia material with a higher biaxial flexural strength, the fracture load values were increased from 751 to 838 N, but more implant fractures occurred. The position within the zirconia disk did not influence the fracture load. Conclusions: A connector size of 9 mm2 and a zirconia material with a lower strength should be considered when designing ICFDPS on zirconia implants to reduce the risk of fractures along the intraosseous implant portion.