Introduction: Non-pharmaceutical interventions (NPIs) are used to reduce transmission TRANS of SARS coronavirus 2 (SARS-CoV-2) that causes coronavirus disease MESHD 2019 (COVID-19). However, empirical evidence of the effectiveness of specific NPIs has been inconsistent. We assessed the effectiveness of NPIs around internal containment and closure, international travel TRANS restrictions, economic measures, and health system actions on SARS-CoV-2 transmission TRANS in 130 countries and territories. Methods: We used panel (longitudinal) regression to estimate the effectiveness of 13 categories of NPIs in reducing SARS-CoV-2 transmission TRANS with data from January - June 2020. First, we examined the temporal association between NPIs using hierarchical cluster analyses. We then regressed the time-varying reproduction number TRANS (Rt) of COVID-19 against different NPIs. We examined different model specifications to account for the temporal lag between NPIs and changes in Rt, levels of NPI intensity, time-varying changes in NPI effect and variable selection criteria. Results were interpreted taking into account both the range of model specifications and temporal clustering of NPIs. Results: There was strong evidence for an association between two NPIs (school closure, internal movement restrictions) and reduced Rt. Another three NPIs (workplace closure, income support and debt/contract relief) had strong evidence of effectiveness when ignoring their level of intensity, while two NPIs (public events cancellation, restriction on gatherings) had strong evidence of their effectiveness only when evaluating their implementation at maximum capacity (e.g., restrictions on 1000+ people gathering were not effective, restrictions on <10 people gathering was). Evidence supporting the effectiveness of the remaining NPIs (stay-at-home requirements, public information campaigns, public transport closure, international travel TRANS controls, testing, contact tracing TRANS) was inconsistent and inconclusive. We found temporal clustering between many of the NPIs. Conclusion: Understanding the impact that specific NPIs have had on SARS-CoV-2 transmission TRANS is complicated by temporal clustering, time-dependent variation in effects and differences in NPI intensity. However, the effectiveness of school closure and internal movement restrictions appears robust across different model specifications taking into account these effects, with some evidence that other NPIs may also be effective under particular conditions. This provides empirical evidence for the potential effectiveness of many although not all the actions policy-makers are taking to respond to the COVID-19 pandemic.