Background: Australia has a high rate of antibiotic use. Government policy interventions are one strategy to optimise the use of antibiotics. On 1 April 2020, the Australian Government Department of Health introduced a policy intervention to increase the quality use of four antibiotics. Objectives: To assess if the government policy intervention improved the appropriate supply of the four antibiotics amoxicillin, amoxicillin-clavulanic acid, cefalexin and roxithromycin. Method: This study employed a retrospective cohort study design comparing a 10% sample (n = 345,018) of four antibiotics prescribed and dispensed in Australia during a three-month period (May, June, July) in 2019, and again in 2020 (after the policy intervention). The 10% sample of PBS data was obtained from the Australian Government Department of Health. Descriptive statistics, bivariate and multivariable logistic regression analysis were carried out. Results: The results suggest the policy change improved the appropriate supply of original prescriptions in 2020 compared to 2019 OR = 1.75 (95% CI = 1.68–1.82, p < 0.001), and appropriate supply of repeat prescriptions OR = 1.56 (95% CI = 1.25–1.96, p < 0.001). In 2020, the proportion of appropriate supply of original prescriptions increased by an absolute difference of 1.8% (95% CI = 1.6–1.9%; P < 0.001), and appropriate supply of repeat prescriptions increased by 3.9% (95% CI = 2.2–5.5%; P < 0.001). The total number of antibiotic prescriptions prescribed and dispensed in 2019 (N = 219,960) reduced in 2020 (N = 125,058) after the policy intervention. Conclusion: The study provides evidence for the impact of a government policy intervention to improve the appropriate supply of antibiotics, although some of the reduction in antibiotic use was likely due to the concomitant COVID-19 pandemic. Further research is required to assess the impact of the intervention outside a pandemic.