Introduction: Open tibial fractures are complex injuries with variable outcomes that significantly impact patients’ lives. Surgical debridement is paramount in preventing detrimental complications such as infection and non-union; however, the exact timing of debridement remains a topic of great controversy. The aim of this study is to evaluate the association between timing of surgical debridement and outcomes such as infection and non-union in open tibial fractures. Materials and Methods: We performed a systematic review and meta-analysis of the literature to capture studies evaluating the association between timing of initial surgical debridement and infection or non-union, or other reported outcomes. We searched the MEDLINE, PubMed Central, EMBASE, SCOPUS, Cochrane Central and Web of Science electronic databases. Our methodology was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Cochrane handbook for systematic reviews of interventions. Results: The systematic review included 20 studies with 10,032 open tibial fractures. The overall infection rate was 14.3% (314 out of 2193) and the overall non-union rate 14.2% (116 out of 817). We did not find any statistically significant association between delayed debridement and infection rate (OR = 0.87; 95% CI, 0.68 to 1.11; p = 0.23) or non-union rate (OR = 0.70; 95% CI, 0.42 to 1.15; p = 0.13). These findings did not change when we accounted for the effect of different time thresholds used for defining early and late debridement, nor with the Gustilo–Anderson classification or varying study characteristics. Conclusion: The findings of this meta-analysis support that delayed surgical debridement does not increase the infection or non-union rates in open tibial fracture injuries. Consequently, we propose that a reasonable delay in the initial debridement is acceptable to ensure that optimal management conditions are in place, such that the availability of surgical expertise, skilled staff and equipment are prioritised over getting to surgery rapidly. We recommend changing the standard guidance around timing for performing surgical debridement to ‘as soon as reasonably possible, once appropriate personnel and equipment are available; ideally within 24-h’.