〔Abstract〕 Objective To evaluate the comparative clinical outcomes of zero-profile interbody fusion (Zero-P) and traditional anterior cervical discectomy and fusion with titanium plate (ACDF- plate) for three-level cervical spondylosis, providing a reference to optimize surgical strategies for three-level cervical spondylosis. Methods In this retrospective comparative study, 113 patients were included and assigned to either the Zero-P group (n=51) or the ACDF-plate group (n=62) according to their surgical approaches. Clinical outcomes were evaluated and compared between the two groups using operative time, intraoperative blood loss, length of hospital stay, visual analog scale (VAS) scores, cervical range of motion (ROM), neck disability index (NDI), Cervical Disability Index (CDI), Japanese orthopaedic association (JOA) scores, and postoperative complication rates. Results Compared with the ACDF-plate group, the Zero-P group had a shorter operative time and less intraoperative blood loss (P<0.05); the neck pain VAS score was lower on the 1st day and 1st week after surgery (P<0.05); the cervical flexion range of motion was higher at 1 month after surgery (P<0.05); the JOA score was higher at 3 months after surgery, while the NDI and CDI scores were lower (P<0.05); the total incidence of complications (11.76%) was significantly lower than that in the plate fixation group (35.48%), and the incidence of neck foreign body sensation/stiffness was lower (P<0.05). Conclusion Zero-P not only demonstrates safety and efficacy comparable to the ACDF-plate, but also highlights the significant value of the minimally invasive concept in facilitating early recovery. Both procedures have their respective emphasis on biomechanical maintenance and minimally invasive benefits, providing a clear evidence-based reference for individualized and precise surgical decision-making in three-level cervical spondylosis.