Purpose: To investigate the anti-caries effects of the school-based fluoride varnish (FV) application at 3-month intervals and weekly fluoride mouthrinsing (FMR) on primary teeth and to evaluate the anti-microbial effects of FV or FMR on cariogenic bacteria among Myanmar children. Materials and Methods: A 6-month interventional study was conducted on 234 schoolchildren who were divided into three groups: group A received FV application at 3-month intervals, group B received weekly FMR, and group C received no fluoride application. A clinical oral examination and caries risk tests were performed at baseline and the 6-month follow-up. Results: Caries prevalence and the debris score did not change statistically significantly from baseline to the 6-month follow-up in all groups, whereas the dmfs score statistically significantly increased in group C (p = 0.001). The plaque and saliva scores of Dentocult SM statistically significantly decreased in group A (p = 0.049 and p = 0.006), but those scores statistically significantly increased in group C (p = 0.001 and p = 0.014) after six months. On the other hand, no statistically significant changes were observed in group B. Although the Cariostat scores decreased from baseline to the 6-month follow-up in group A and group B, but increased in group C, no statistically significant differences were observed in any of the groups. Conclusion: Better anti-microbial effects were obtained for children who received FV application than for those who received FMR, but no statistically significant difference existed between the anti-caries effects of these two approaches.