Background: Despite the availability of a highly efficacious vaccine, varicella outbreaks are still being reported globally. In this study, we evaluated the real-world effectiveness of varicella vaccination among children between the ages of 1 and 18 years old during the period 2017 to 2019 in Qatar. Methods: A matched case–control study was conducted that included all reported varicella-infected children who visited the primary healthcare system in Qatar from January 2017 to December 2019. The cases were children under the age of 18 years who were clinically diagnosed with varicella. The controls were of the same age, who visited the Primary Health Care Corporation (PHCC) during 2017–2019 with a skin rash where varicella infection was ruled out. The data on varicella vaccination for each participant were obtained from the electronic database in the PHCC during the study period. Results: We included 862 cases of varicella and 5454 matched controls, with a median age of 8 years (IQR 3–12); 47.4% were female and almost 50% were of Qatari nationality. The year 2019 had the highest varicella infection count with a total of 416 cases. The cases were less likely to be vaccinated against varicella, with approximately a quarter (25.6%) of cases and 36.7% of the controls having either one or two doses of the vaccine (p < 0.001). Compared to not being vaccinated, a single dose vaccination showed a 56% reduction in the odds of varicella infection [OR 0.44, 95% CI: 0.34–0.55; p < 0.000], and a two-dose vaccination showed an 86% reduction in the odds of varicella infection [OR 0.13, 95% CI: 0.06–0.29; p < 0.000]. Conclusion: In this multicultural setting, a two-dose varicella vaccination shows reasonable protection against varicella infection.