Zygomatic implants are used in patients with maxillary defects to improve the retention and stability of obturator prostheses, thereby securing good oral function. Prosthetic-driven placement of zygomatic implants is even difficult for experienced surgeons, and with a free-hand approach, deviation from the preplanned implant positions is inevitable, thereby impeding immediate implant-retained obturation. A novel, digitalized workflow of surgical planning was used in 10 patients. Maxillectomy was performed with 3D-printed cutting, and drill guides were used for subsequent placement of zygomatic implants with immediate placement of implant-retained obturator prosthesis. The outcome parameters were the accuracy of implant positioning and the prosthetic fit of the obturator prosthesis in this one-stage procedure. Zygomatic implants (n = 28) were placed with good accuracy (mean deviation 1.73 ± 0.57 mm and 2.97 ± 1.38° 3D angle deviation), and in all cases, the obturator prosthesis fitted as pre-operatively planned. The 3D accuracy of the abutment positions was 1.58 ± 1.66 mm. The accuracy of the abutment position in the occlusal plane was 2.21 ± 1.33 mm, with a height accuracy of 1.32 ± 1.57 mm. This feasibility study shows that the application of these novel designed 3D-printed surgical guides results in predictable zygomatic implant placement and provides the possibility of immediate prosthetic rehabilitation in head and neck oncology patients after maxillectomy.