Background The optimal surgical approach for managing multilevel cervical disc degeneration remains debatable, particularly regarding the comparative efficacy and safety of hybrid surgery (HS) versus anterior cervical discectomy and fusion (ACDF). This meta-analysis aimed to evaluate the efficacy and safety of HS compared to ACDF in patients with multilevel cervical degenerative disc disease (CDDD). Methods This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four databases were searched for studies published between January 2000 and December 2024 comparing HS and ACDF in multilevel CDDD. A random-effects model was used to analyze the visual analog scale scores, neck disability index, C2–C7 range of motion (ROM), superior and inferior adjacent segments ROM, adjacent segment degeneration (ASD), heterotopic ossification (HO), intraoperative blood loss, operation time, and complication rates. Subgroup and sensitivity analyses were performed. Evidence quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. Results Nine studies (eight observational and one randomized controlled trial), including 394 patients, were analyzed. The postoperative C2–C7 ROM was significantly greater after HS than after ACDF. The ROM at superior and inferior adjacent segments was significantly lower after HS than after ACDF. No significant differences were observed in the visual analog scale scores, neck disability index, adjacent segment degeneration, heterotopic ossification, intraoperative blood loss, operation time, or complication rates. Conclusions Compared to ACDF, HS better preserves C2-C7 cervical mobility and reduces adjacent segments ROM but does not lower ASD incidence or improve clinical outcomes or complication rates compared to ACDF.