There is a significant challenge in responding to second waves of COVID-19 cases, with governments being hesitant in introducing hard lockdown measures given the resulting economic impact. In addition, rising case numbers reflect an increase in coronavirus transmission some time previously, so timing of response measures is highly important. Australia experienced a second wave from June 2020 onwards, confined to greater Melbourne, with initial social distancing measures failing to reduce rapidly increasing case numbers. We conducted a detailed analysis of this outbreak, together with an evaluation of the effectiveness of alternative response strategies, to provide guidance to countries experiencing second waves of SARS-Cov-2 transmission. An individual-based transmission model was used to (1) describe a second-wave COVID-19 epidemic in Australia; (2) evaluate the impact of lockdown strategies used; and (3) evaluate effectiveness of alternative mitigation strategies. The model was calibrated using daily diagnosed case data prior to lockdown. Specific social distancing interventions were modelled by adjusting person-to-person contacts in mixing locations. Modelling earlier activation of lockdown measures are predicted to reduce total case numbers by more than 50%. Epidemic peaks and duration of the second wave were also shown to reduce. Our results suggest that activating lockdown measures when second-wave case numbers first indicated exponential growth, would have been highly effective in reducing COVID-19 cases. The model was shown to realistically predict the epidemic growth rate under the social distancing measures applied, validating the methods applied. The timing of social distancing activation is shown to be critical to their effectiveness. Data showing exponential rise in cases, doubling every 7–10 days, can be used to trigger early lockdown measures. Such measures are shown to be necessary to reduce daily and total case numbers, and the consequential health burden, so preventing health care facilities being overwhelmed. Early control of second wave resurgence potentially permits strict lockdown measures to be eased earlier.