Objective Meta-analysis was used to evaluate the efficacy and safety of anti-tuberculosis fixed-dose combination (FDC) in the treatment of primary tuberculosis. Methods A computerized search was conducted to identify publicly available literature on the treatment of primary tuberculosis with anti-tuberculosis fixed-dose combinations in PubMed, Web of Science, China Knowledge, Wanfang Data Knowledge Service Platform, and Wipu. com databases for the period from the time of database creation to October 2024. The keywords included “tuberculosis”, “chemotherapy”, “fixed-dose combination”, “tuberculosis”, “Fixed-dose Combination”. The experimental subjects were patients with primary tuberculosis, and the experimental group was treated with anti-tuberculosis FDC, while the control group was treated with traditional plate drugs. The information of the included literature was extracted, including the first author, year of publication, sample size, etc.; Cochrane evaluation method was used to evaluate the quality of the included literature; the main outcome indicators included sputum conversion at the end of February and at the end of the treatment, treatment efficiency, incidence of adverse effects, shadow absorption, and cavity closure. Meta-analysis was performed using Stata MP 18 and RevMan 5.4 software; Finally, publication bias was analyzed using Begg′s and Egger′s tests. Results Nine papers were finally included, containing a total of 4 680 cases in the experimental group and 4 712 cases in the control group, and the selection bias of each paper was low risk. Meta-analysis showed that the sputum conversion at the end of February in the experimental group (RR=1.05, 95% CI: 1.03-1.07), sputum conversion at the end of treatment (RR=1.04, 95% CI: 1.03-1.05), treatmentefficiency (RR=1.04, 95% CI: 1.02-1.05), shadow absorption rate (RR=1.07, 95% CI: 1.04-1.09), and cavity closure rate (RR=1.04, 95% CI: 1.02-1.05) were higher than those of the control group; the incidence rate of adverse reactions (RR=1.01, 95% CI: 0.93-1.09) was not statistically significant; the funnel plot results showed that the publication bias of the above effect indicators were small. Conclusion Anti-tuberculosis FDC increased the sputum conversion rate, treatment efficiency, shadow absorption rate, and cavity closure rate at the end of 2 months and at the end of treatment when compared with the quadruple anti-tuberculosis regimen alone for the treatment of first-treatment tuberculosis; there was little difference in the incidence of adverse reactions.