Orthodontic space closure of extraction sites can be initiated early, within 1-week post-extraction, or it can be delayed for a month or more. This systematic review aimed to evaluate the effect of early versus delayed initiation of space closure after tooth extraction on the rate of orthodontic tooth movement. Unrestricted search of 10 electronic databases was conducted until September 2022. Randomized controlled trials (RCTs) investigating the initiation time of space closure of extraction sites in patients undergoing orthodontic treatment were included. Data items were extracted using a pre-piloted extraction form. The Cochrane's risk of bias tool (ROB 2.0) and the Grading of Recommendations, Assessment, Development, and Evaluation approach were used for quality assessment. Meta-analysis was undertaken if there are at least two trials reporting the same outcome. Eleven RCTs met the inclusion criteria. Meta-analysis revealed that early canine retraction resulted in a statistically significant higher rate of maxillary canine retraction when compared to delayed canine retraction [mean difference (MD); 0.17 mm/month, 95% CI: 0.06 to 0.28, P = 0.003, 4 RCTs, moderate quality]. Duration of space closure was shorter in the early space closure group, but not statistically significant (MD; 1.11 months, 95% CI: -0.27 to 2.49, P = 0.11, 2 RCTs, low quality). The incidence of gingival invaginations was not statistically different between early and delayed space closure groups (Odds ratio; 0.79, 95% CI: 0.27 to 2.29, 2 RCTs, P = 0.66, very low quality). Qualitative synthesis found no statistically significant differences between the two groups regarding anchorage loss, root resorption, tooth tipping, and alveolar bone height. Based on the available evidence, early traction within the first week after tooth extraction has a minimal clinically significant effect on the rate of tooth movement compared to delayed traction. Further high-quality RCTs with standardized time points and measurement methods are still needed. PROSPERO (CRD42022346026).