Background Indoor residual spraying (IRS) is one of the key interventions recommended by World Health Organization in preventing malaria infection. We aimed to conduct a systematic review and meta-analysis of global studies about the impact of IRS on malaria control. Method We searched PubMed, Web of Science, Embase, and Scopus for relevant studies published from database establishment to 31 December 2021. Random-effects models were used to perform meta-analysis and subgroup analysis to pool the odds ratio (OR) and 95% confidence interval (CI). Meta-regression was used to investigate potential factors of heterogeneity across studies. Results Thirty-eight articles including 81 reports and 1,174,970 individuals were included in the meta-analysis. IRS was associated with lower rates of malaria infection (OR = 0.35, 95% CI: 0.27–0.44). The significantly higher effectiveness was observed in IRS coverage ≥ 80% than in IRS coverage < 80%. Pyrethroids was identified to show the greatest performance in malaria control. In addition, higher effectiveness was associated with a lower gross domestic product as well as a higher coverage of IRS and bed net utilization. Conclusions IRS could induce a positive effect on malaria infection globally. The high IRS coverage and the use of pyrethroids are key measures to reduce malaria infection. More efforts should focus on increasing IRS coverage, developing more effective new insecticides against malaria, and using multiple interventions comprehensively to achieve malaria control goals.