Objectives: The varicella vaccine (VarV) produced by Sinovac (Dalian) obtained World Health Organization (WHO) prequalification in November 2022. However, no direct comparative studies have been conducted between VarV and other WHO-prequalified varicella vaccines. The study aimed to assess the immunogenicity and safety of Sinovac’s VarV compared with Merck Sharp & Dohme’s (MSD) VARIVAX^® (Moorgate, London, UK) following a single dose administration. Methods: This Phase III, randomized, double-blind, active-controlled, non-inferiority trial was conducted in the Philippines. Healthy children aged 12 to 15 months were enrolled. Eligible participants were randomly assigned (1:1) to receive a single dose of varicella vaccine either manufactured by Sinovac (Test group) or MSD (Active control group). Immunogenicity was evaluated 6 weeks after vaccination by enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity endpoint was seroresponse rate 6 weeks after vaccination. Seroresponse rate was defined as varicella-zoster virus (VZV) antibody concentration ≥ 10 mIU/mL in participants who were seronegative (antibody concentration < 10 mIU/mL) at baseline. The secondary endpoint was the corresponding geometric mean concentration (GMC). Adverse events (AEs) and serious adverse events (SAEs) were monitored for 6 weeks after vaccination. Results: Among the 484 participants analyzed, the seroresponse rates 6 weeks after vaccination were 98.85% and 98.88% in the Test group and Active control group, respectively, with a difference of −0.03% (95% CI: −3.10%, 2.99%), which exceeded the predefined non-inferiority margin of −10%. The corresponding GMCs were 35.73 mIU/mL and 37.34 mIU/mL, respectively, with the ratio of 0.96 (95% CI: 0.86, 1.06), also exceeding the predefined non-inferiority margin of 0.67. Furthermore, the incidence of adverse reactions (ARs) in the Test group was lower than that in the Active control group (38.08% vs. 55.51%). Conclusions: Sinovac’s VarV demonstrated non-inferior immunogenicity to WHO-prequalified comparator vaccine (VARIVAX^®) and favorable safety profile. These findings indicated that VarV (Sinovac, Beijing, China) met WHO standards for varicella vaccine evaluation, supporting its global use consideration.